WO2010146601A1

WO2010146601A1 - Rapid dissolvable oral film for delivering herbal extract/s with or without other pharmaceutically active agents

Info

Publication number: WO2010146601A1
Application number: PCT/IN2010/000404
Authority: WO
Inventors: Vinita Vijay Kale; Amarnath Bhaskarrao Wattamwar; Anwar Siraj Daud
Original assignee: Unijules Life Sciences Ltd
Priority date: 2009-06-15
Filing date: 2010-06-15
Publication date: 2010-12-23
Also published as: WO2010146601A4

Abstract

The invention comprises an oral film, single layer or multilayer, for delivering an active ingredients, herbal or non-herbal, to oral cavity, wherein the said oral film requires at least a delay of about 5 seconds after coming in contact with oral mucosa to stick to the mucosa surface in contact and rapidly dissolves thereafter. The said oral film takes about 1 to 1.15 minutes for dissolution in an oral cavity after hydration. The said film is having low hygroscopicity and high mucoadhesivity, absorbs less than 5% moisture, and preferably less than 2%, of its weight and is stable at 75 % RH (relative humidity). Mucodhesivity and higher dissolving rate is imparted by hydroxy alkyl derivative of cellulose, preferably by Hydroxypropyl Methyl Cellulose, and low- hygroscopicity is imparted by polyvinyl alcohol polyethylene glycol graft polymer, preferably by Kollicoat^® IR. Disclosed are single and multilayer films carrying herbal extracts from all botanical parts of plants, by several methods of extraction as well as some non-herbal actives that are useful as treatments for disease indication and processes for making them and bearing optional identification marks.

Description

RAPID DISSOLVABLE ORAL FILM FOR DELIVERING HERBAL EXTRACT/S WITH OR WITHOUT OTHER PHARMACEUTICALLY ACTIVE AGENTS.

TECHNICAL FIELD

The present disclosed invention relates to a method of preparation of rapid dissolving single or multiple layered edible film formulation with improved stability and water resistance characteristics for delivering single or more than one herbal extracts / with or without one or more pharmaceutically active agents.

BACKGROUND OF INVENTION

Ayurveda is a well established long tested and proven science of medicine. The Ayurveda enlightens on prescribing various hetbs for treatment of many diseases and disorders of mamnrils I he herbal formulations includes Asava. Arishth? C huma, Gutika, Kadha, Prasha, Vati. Paka, Avaleha, Ghrita, Murabba, Sharbat, Suffof, Araq, Habba, Rouqhun, Qurs. which suffer a common disadvantage of lack of patient compliance as the formulations like Churaas are needed to be taken in bulk amount with glassful of water. Modern foπnulation systems like herbal tablets and capsules have increased the patient compliance. However, if the dose of herb is more, then more than one tablets/ capsules need to be taken at the same time that too are required to be taken twice or thrice a day. In such prescription schedule of medication becomes hectic for patient, and ultimately patients won't comply with the medication. An easy method of delivering herbal foπnulation has been invented in the form of rapid dissolving single or multiple layer film carrying herbal extract/s with or without other pharmaceutically active agents in the formulation. PRIOR ART

In U.S. Pat No.6, 177, 096 Bl, Zerbe et al. discloses compositions applicable to the oral cavity comprising at least one water-soluble polymer, at least one polyalcohol, and at least one cosmetically or pharmaceutically active ingredient, wherein the composition has mucoadhesive properties. The film disclosed particularly is a single layer film

In U.S. Pat No.7, 182, 964 B2 discloses a rapidly dissolving film comprising, amongst other ingredients, of xanthones derived from a mixture of pulp and pericarp of fruit of Garcinia mangostana L. plant.

In the patent US 4925670, Schmidt et al. have disclosed the formulation in the form of film in which a film like carrier material having active medicament is coated on release paper, film or foil, and the films containing actives are removed in a dose wise manner from the carrier^ material after subdivision into dosage form at the time of administration. The said particular_.,:^ invention thus comprises an orally dissolvable film that is packed along with carrier and relates ^■ to a single polymeric film.

In patent US7025983 B2, Leung et al. have disclosed a film and method for preparing a film that;, carries an electrolyte and at least two essential oils selected from the group consisting of thymol, methyl salicylate, eucalyptol, and menthol with at least one stabilizing agent selected from the group consisting of xanthan gum, locust bean gum, carrageenan, guar gum and mixtures thereof to provide a film-forming mixture.

In United States patent applications disclosed pullulan free films with an effective amount of an antimicrobial agent wherein the antimicrobial agent which comprises cinnamaldehyde in US 20040086546; and cardamom oil in US 20040253192. and carvacrol in 20040253278 .

In United States patent application No. 2003023560.6; Kenneth H. Nussen disclosed a method comprising: mixing one or more natural film forming agent(s) with at least one of a vitamin, a mineral and an herb to form a composition; drying the composition on a substrate to form an edible film. Tea extract is used here as herb extract.

In the United States patent application No. 20040180077 Riker et al., disclosed rapidly dissolving edible strips for treatment of obesity comprising one or more herbal extract including caffeine, green tea extract, theobromine, ginseng root, theonine, arginine and mixtures thereof.

Most of the Ayurvedic and other traditional systems of medicines use multiherbal preparations for treatment, these multiherbal preparations have interaction problems. For avoiding such consequences of interactions spatial separation minimizing physical contact is required.

Despite the known use of rapidly dissolving edible films and their benefits over predecessor technologies for oral ingestion and documented benefits of herbs and pharmaceutically active ingredients, they are highly hygroscopic, due to which they stick to each other during storage and- they also present problem in accurate placing in the mouth, because while the film is beings maneuvered in the mouth cavity for placement at most appropriate place, it is most probable, that it comes in at least a momentary contact with wet inner surface of mouth and that is enough to make it stick immediately to it, start dissolving and prevents in fine tuning its position to preferred location inside the mouth. At the same time, the prior art files that were not hygroscopic, they have a problem of allowing being rejected / discarded / spit out by non- compliant patients, such as children, after delivery of the film in their oral cavity. There is, thus, a need of an oral rapidly dissolving film that shall not stick to inner surface of the mouth as soon as it is placed inside, giving sufficient time to maneuver inside the oral cavity to place it at desired location, but stick soon thereafter at the location that is finally located by the said maneuver, not allowing a voluntary spitting out by the patient.

SUMMARY OF INVENTION

The invention comprises an oral film for delivering an active ingredients to oral cavity, wherein the said oral film requires at least a delay of about 5 seconds after coming in contact with oral mucosa to stick to the mucosa surface in contact and rapidly dissolves thereafter. The said oral film comprises a herbal or a non-herbal active ingredients, The said oral film may be a single layer film or a multilayer film. The said oral film takes about 1 to 1.15 minutes for dissolution in an oral cavity after hydration.

In one embodiment, the oral rapid dissolving film for oral delivery of this invention has an active ingredients wherein the said film is having low hygroscopicity and high mucoadhesivity.

An oral film of this invention in one embodiment, absorbs less than 5% moisture, and preferably less than 2%, of its weight and are stable at 75% RH (relative humidity).

In another embodiment, in oral film of this invention, the mucodhesivity and higher dissolving rate is imparted by hydroxy alkyl derivative of cellulose, preferably by Hydroxypropyl Methyl Cellulose, and low- hygroscopicity is imparted by polyvinyl alcohol polyethylene glycol graft polymer, preferably by Kollicoat^® IR.

In one aspect of this invention, polyvinyl alcohol polyethylene glycol graft polymer, is present in the film composition to the extent of between 5% and 50%, more preferably 5% - 40% by weight of the film composition.

In another aspect of this invention, the said other water soluble polymer present in the film formulation in combination with graft polymer are selected from group consisting of, hydroxypropyl methyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, carboxy methyl cellulose, guar gum, carboxy methyl guar gum, carboxy methyl locust bean gum, acacia gum, arabic gum, pectin, chitosan, mixtures thereof and the like polymers to the extent of between 10% and 50% by weight of the film composition. The said polyvinyl alcohol polyethylene glycol graft polymer has a viscosity in the range of 130 to 190 millipascal seconds, when viscosity of a 20 % solution is found at 23 ⁰C , more preferably 150 to 170 millipascal seconds when viscosity of a 20 % solution is found at 23°C. The oral film of this invention comprises of a polyvinyl alcohol polyethylene glycol graft polymer having low viscosity and a cellulose derivative as film fonning polymers and additives. The said additives comprise an additional one more water soluble polymer, a surfactant, a stabilizing agent, an emulsifier, a plasticizer, a water soluble sugar, a binder, a sweetener, a flavors, a plasticizer, an antioxidant, a volatile oil and combinations thereof.

In one embodiment of an oral film of this invention, the herbal extract ingredient is prepared from a botanical part of the plant that comprises at least whole or part of a root, a stem, a bark, a leaf, a flower, a fruit, a seed or whole plant. The extraction process can be one form of various types. Illustrative process comprises at least one from group of processes comprising cold extraction technique, soxhlet extractor, making a decoction, supercritical extraction, microwave extraction using a variety of different extraction solvents. Solvents used in illustrated processes include a solvent selected from the group ethanol, methanol, acetone, acetonitrile. chloroform, , water, hydroalcoholic mixture and isopropyl alcohol. ^■ -r

The active ingredients comprised, as % of weight of the film, between a range of 10% to 65%, more preferably between a range of 10% to 45%.

Illustrated single films, each of which are embodiments of this invention, comprise anti-emetic, comprising extracts of Zingiber officinale Roxb. unci Piper longum Linn at about 10 % each by weight of the film composition, memory support film comprising incorporation of extracts of Bacopa monnieri Linn and Centella asiatica Linn at about 10 % each by weight of the film composition, antidiabetic film comprising incorporation of extract of Momordica charantia Linn. at about 15 % each by weight of the film composition, antidiabetic film comprising incorporation of extract of Azadirachta indica A Juss. at about 15 % each by weight of the film composition, antistress film comprising incorporation of extract of comprising extracts of Withania somnifera Dunal., Bacopa monnieri Linn., Nardostachys jatamansi DC or at about 6, 9 and 5 % each respectively by weight of the film composition, diuretic film comprising incorporation of extract of comprising extracts of Boerhavia diffusa Linn., Tribulus terrestris Linn' at about 10 % each by weight of the film composition, hepatoprotective film comprising incoiporation of extract of comprising extracts of Picrorhiza kurroa Roy Ie ex Benth., Phyllanthus niruri Linn, at about 7 % and 13 % each respectively, by weight of the film composition, antidiarrhoeal film comprising incorporation of extract of Holarrhena antidysentrica (Roth) A. DC, Euprhorbia hirta Linn, at about 15 % and 5 % each respectively by weight of the film composition, galactogogue film comprising incorporation of extract of Asparagus racemosiis Willd., Euphorbia hitra Linn., Pueraria tuberose DC, Trigonella foenum- graceum Linn., Leptadenia raticulata, Withania somnifera Dunal. at about 7%, 2.5%, 4%, 4%, 3% and 2% each respectively by weight of the film composition, cardiotonic film comprising incorporation of extract of Tribulus terrestris Linn., Terminalia arjuna, Pueraria tuberose DC, Trigonella foenum- graceum Linn., Leptadenia raticulata, Withania somnifera Dunal at about 7%, 13%, 4%, 4%, 3% and 2% each respectively by weight of the film composition.

An illustrated embodiment of a multilayer film of claim 12 comprised extracts of Zingiber officinale Roxb. and Piper longum Linn.; preferably containing the active ingredient in a range of about 20% and 2% respectively by weight of the film composition.

An illustrated multilayer embodiment of film comprising non-herbal pharmaceutical active comprised extract of chlorpheniramine maleate and Phenylephrine preferably containing the active ingredient in a range of about 20% and 2% respectively by weight of the film composition.

Invention also comprises a process of making an oral dissolving film comprising forming the same film by using a polyvinyl alcohol polyethylene glycol graft polymer having low viscosity and a cellulose derivative as film forming polymers and additives for forming the film. The said process of making single layer or multilayer film comprises selecting at least one step as per requirement of product from the following: (a) formation of slurry of an extract/pharmaceutically active ingredient added to a film forming composition in aqueous or any suitable solvent, (b) debubbling of formed slurry, Casting of slurry done by one of any methods selected from blade over belt method, spray cast method, slot die coating, comma blade process, pouring on substrate method, (c) drying of casted wet film at an elevated temperature, preferably at a temperature of about 40 - 70 ⁰C, (d) cooling of casting line along with dry film at the end of casting line, so as to reduce recoiling of film, (e) for making a multilayer film, adding one or more of an inert or / and active containing layer on primary film by gluing or casting, optionally compacting by passing through a roller, (f) drying of multiple layer film, (f) cooling of casting line along with dry film at the end of casting line, so as to reduce recoiling of film, (g) cutting and slitting of film strips in different size and shape to form a readily, unobtrusively consumable thin film formulation.

A process of the said film foπning composition comprises, as per requirement and option, an additional one more water soluble polymer, a surfactant, a stabilizing agent, an emulsifiex, a * plasticizer, a water soluble sugar, a binder, a sweetener, a flavor, a plasticizer, an antioxidant, -a<> volatile oil and combinations thereof.

In the process of invention, the binder illustrated for gluing the films or incorporating in the ^■ secondary film for making multi layer films is Polyoxyethylene. Any other binder achieving same job can also be used within the scope of this invention.

The film of this invention also may have unique identification markings on the surface of the films, both artistic and informational markings comprising company name or symbol, product code, product name, potency of the product, calendar wise or day wise prescription schedule printed or embossed on the film surface, printed line printed or embossed on the film or film portions separated by perforations are provided for taking exactly Vi, 1/3 , !4 portion of film for taking exact dose as prescribed. DETAILED DESCRIPTION OF INVENTION

In one aspect of the film of this invention takes a about 5 seconds to hydrate so that adequate time is available for its maneuvering inside oral cavity for locating it at preferred location, but rapidly dissolves after hydration. Total time needed to disintegrates is about 1 min tol.15 min.

The film of this invention further contains one or more herbal or non-herbal pharmaceutical actives, is single or multilayered, and mucoadhesive. The film of this invention is useful for systemic absorption.

The present surface dissolving film, which adheres to mucosal surface upon application exhibits very low hygroscopicity and high mucoadhesivity. For the purpose of this specification a "low- hygroscopicity" composition is intended to mean a composition which absorbs less than 5% moisture and preferably less than 2% of its weight and are stable at 75% RH. High mucoadhesivity means the device adheres to the mucosal surface and active is absorbed . substantially at the point of adhesion within the oral cavity. In the examples illustrated in this invention, the mucodhesivity is imparted by hydroxy alkyl derivative of cellulose such as Hydroxypropyl Methyl Cellulose and higher dissolving rate. Low- hygroscopicity is imparted by polyvinyl alcohol polyethylene glycol graft polymer such as Kollicoat^® IR. Low hygroscopicity increases the stability, decreases interaction of multiple actives and also imparts fast dissolving characteristics to the dosage form as the low moisture prevents Hydrolytic cleavage of the drugs entrapped in the film.

The present mucosal surface dissolving film exhibits a unique property of getting hydrated only after few seconds upon exposure to moisture on account of slow initial hydration of the film matrix. Due to this specific low hygroscopicity of the present formulation, the formulation can be packed in the form of multiple unit dosage packaging without being affected by the atmospheric moisture provides the sufficient time to accurately place the dosage form at the intended position (ex. buccal dosing, sublingual dosing etc.). Rejection of the administered dosage is required to be ensured in pediatric and psychotic patients, as these patients mostly spit the dosage after administration. The present surface dissolving film initially hydrates slowly but the film upon application to a particular desired site adheres to the oral mucosa after the initial hydration and thereby it can not be easily spit out.

In one of the embodiment the film forming agents include hydroxyalkyl cellulose, Kollicoat^® IR (polyvinyl alcohol polyethylene glycol graft polymer) with or without other hydrocolloids / stabilizers.

Polyvinyl alcohol polyethylene glycol graft polymer used in this invention has, preferably, a viscosity in the range of (130-190), more preferably of 162 millipascal seconds (mPa-s) as deteπnined on a 2 % by weight aqueous solution of the polyvinyl alcohol polyethylene glycol graft polymer at 23° C by Brookfield viscometer. Polyvinyl alcohol polyethylene glycol graft polymer is available commercially from the BASF Chemical Company under the trade , designation Kollicoat^® IR. The Kollicoat^1® IR is incorporated in the film composition in amounts" ranging from about 10 to about 50% by weight and preferably about 12 to about 40% by weight.

It is found to be critical to the present invention that one of such water soluble polymer HPMC . having a viscosity in the range of about 1 to about 40 millipascal seconds (mPa-s) as determined on a 2% by weight aqueous solution of the HPMC at 23°C can be used. Preferably the HPMC having viscosity of about 3 to about 20(mPa-s) at 2O⁰C can be used. For a given film thickness, lower the viscosity of a HPMC more rapid the dissolution of the film.

In another embodiment of this invention the multiple layer film comprises of film forming agent combined with water soluble hydrocolloids / stabilizers, extract/s, with or without a flavoring agents particularly an essential oil which act as breath freshening agent. The film further comprises of solvent, plasticizing agents, flavoring agents, surfactants, emulsifying agents, antioxidants, preservatives, sweeteners and fragrances. Water soluble cellulose polymers are selected from the group consisting of hydroxypropyl methyl cellulose, hydroxy ethyl cellulose, carboxy methyl cellulose,Pullulan polyvinyl alcohol polyethylene glycol graft polymer and soluble cellulosic polymer, wherein their ratio (with above mentioned polymer (by weight) may vary from about 1 :3 to about 6:2 and preferably about 3.5:1 to about 6: 1.5. The hydrocolloids / stabilizers are selected from the group of polymers derived naturally or semi synthetically, and can comprise one or combination of hydrocolloids selected from amongst guar gum, xanthan gum, locust bean gum, carrageenan, gum tragacanth, pectin, Carboxy methyl guar gum, Carboxy methyl locust bean gum

The film forming agents in the core (primary) film comprises of polyvinyl alcohol polyethylene graft polymer (Kollicoat^® IR), water soluble cellulosic polymer like low viscosity hydroxypropyl methyl cellulose, carboxy methyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, guar gum, carboxy methyl guar gum, carboxy methyl locust bean gum, acacia gum, arabic gum, pectin, chitosan

In one of the embodiment of this invention heibal extract/s is prepared b^ any method ot_' extraction. The term extract as used herein in this particular invention includes all of the many types of preparations containing an effective amount of active ingredient/s produced by biogenesis by the plants from which they are extracted. Thus this particular invention encompasses all possibilities of preparation of extract, thus the extracts can be produced by cold extraction technique, soxhlet extractor, decoction method, supercritical extraction, microwave extraction using a variety of different extraction solvents including, but not limited to ethanol, methanol, acetone, acetonitrile, chloroform, water, hydroalcoholic mixture, isopropyl alcohol and the like. The extract incorporated is also not limited to any specific part of plant, the extract can be derived from any and all parts include flowers, leaves, stem, bark, roots, inflorescence and the like; and in a particular film different proportions of extracts of different parts of the plant could also be incorporated in the film. The film may comprise one extract or when the extracts/ one or more pharmaceutically active ingredients have no incompatibility with each other either for chemical reasons or when the extracts pertains to a pharmaceuticals system where mixing extracts from two or more plants is not barred during preparation and storage of the product, the film comprising more than one extracts can be prepared.

The list of herbs known traditionally for their therapeutic values is very long. Appropriate plant extract compositions for use in the film comprises extract of any medicinal plant including but not limited to Zingiber officinale Roxb., Piper longum Linn., Boswellian serrata Roxb., Vitex negunda Linn., Tinospora codifolia, Curcuma longa Linn., Centella asiatica Linn., Bacopa monnieri Linn., Momordica charantia Linn., Azadirachta indica, Ocimum sanctum, Picrorhiza kurroa Royle ex benth, Withania somnifera, Tribulus terristris Linn., Nardostachys jatamansi, Boerhavia diffusa Linn., Phyllanthus niruri Linn., Cassia angustifolia Vahl., Holarrhena antidysentrica (Roth), Asparagus racemosus Willd., Allivum sativum Linn., Euphorbia hirta Linn., Peuraria tuberosa., Leptadia reticulata, Trigonella foenum-graceum Linn., Miicuna prureins Baker., Terminalia arjuna, Achyranthes bidentatae Wall, Λchyirmthes aspera Linn. Achyranthes prophyristachya Wall, Aconitum napellus Linn, Acorus americaiius, -AcLiaidiu arguta, Actinidia arguta, Actinidia arisanensis, actinidia callosa, Adenophora tetraphylla Radix, Albizia julibrissin, Alisma caniculatum, Alisma orientale, Alpinia magnifera Rose, Alpenia galangal Willd, panax quinquefolium Linn, Asparagusracemosus Willd, Astragalus membranaceus, Atractylodesmacrocephalae, Biota orientalis Semen, Bupleurum Chinese Radix, Chrysanthemum morifolium Flos, chrysanthemum indicum Flos, Cibotium baromet∑, cnidium monnieri, codonopsis pilosula Radix, Coix lachrymal, Cornus officinalis, Crataegus pinnatifida, Cuscuta chinensis Semen, Cynomorium songaricum, Dioscorea bulbifera, Dioscorea opposite Radix, Dioscorea hypoglauca, Drynaria fortune, Eucommia ulmoides, Evodia rutaecarpa, Foeniculum vulgare, Gingko bilobae, Panax ginseng, Gynostemma pentaphyllum Radix, Ligusticum sinesis Radix, Ligusticum wqallichii Radix, Liigustrum lucidum, lilium brownie, Lycium barbarum, Morinda officinalis Radix, Ophiopogonis japonicum, Polygonatum sibiricuin, Polygonum multifori Radix, polyporum umbellatum, Psoralea cordifolia, Pueraria lobata Radix,

I l Rehmania glutinosa Radix, Rhodiola rosea, Rubus chingii, Salvia miltiorrhiza Radix, Schisandra chinensis, Uncaria Rhynchophylla, Zizyphus jejuba, Zizyphus spinosa and the like.

The knowledge of efficacy of the extracts mentioned above arises form traditional knowledge of

Ayurveda. Bhavprakash and Charak Samhita are amongst the ancient scriptures which are considered as authentic source of the said traditional knowledge which is considered to have compiled centuries of practical experience with medicinal applications and science of plants and their extracts. Based on this knowledge the extracts illustrated used here, disease indications on which they are useful and the reference for the knowledge of their efficacy are : Appropriate non-herbal pharmaceutically active ingredients for use in the edible film of the present invention include, but not limited to, one or more than one pharmaceutically active agent comprising Levoctrizine, Prochlorperazine, Folic acid, Methylcobalamine, Cynocobalamine, Voglibose, Clonazepam, Domperidone, Losartan, Amlodipine, Doxazocine, Enalapril, Nebivolol, Locidipine, Prazocine, Terazocine, Glyceryl trinitrate, Nifedipine, Acenocoumarol, Ramipril, Hydroxyzine, Ondanosetron, Trifluoperazine, Bromocriptine, Cobergoline, Selegiline, Triphenidyl HCL. Codergocrine, Fentanyl, Flunarizine, Rizatriptan, Lornoxicam, Tizanidine, Donepezil, Rivastigmiine, Betamethasone, Terazocin, Glimeperide, Finasteride, Salbutamol, Ketotifen, Montelukast, Cetrizine, Clemastine, Cyproheptadine, Pesloratidine, Rupatadine, Methotrexate, Tacrolimus, Sirolimus, Dimethindone, Dutasteride, Tamsulosin, Tolteridone, Indapamide, Fluphenthixol, Resperidone, Alprazolam, Dextromethorphan, and the like.

Additionally the film composition may comprise fast dissolving polymers, plasticizers, sugars, flavors, sweeteners, stabilizing agents antioxidants, preservatives, colours. Flavoring agents that • can be used to prepare the film of the present invention include those known to the skilled artisan, such as natural and artificial flavors.

These flavorings comprise of synthetic flavor oils and flavoring aromatics, and/or essential oils and their mixtures including but not limited to lemon oil, orange oil, lemon grass oil, cinnamon oil, clove oil, ginger oil, spearmint oil, peppermint oil, eucalyptus oil. oil of nutmeg, Mentha piperita (menthol), methyl salicylate , peppermint, vanilla and the like. Generally the flavoring agent is incorporated in the film of the present invention in an amount ranging from about 0.1% to about 8 % by weight and preferably about 0.4% to about 5 % by weight.

Single or multiple numbers of water soluble sugars can be used in the embodiments of the present invention. These agents are well known in the art, which include common food-grade sweeteners such as glucose, dextrose, fructose, lactose, maltose, xylose, sucrose. The concentration used may range from about 1% to about 10% by weight and preferably about 2% to about 8% by weight. Synthetic sweeteners plus, sugar-related compound such as sorbitol, hexitol, Maltitol, xylitol, and mannitol, aspartame, saccharine sodium, sucralfate, alitame, cyclamate, acesulfame trehalose (alpha-D-glucopyranosyl alpha-D-glucopyranoside) are also advantageous as additives in the present invention. The high water soluble sugars present in the film of the present invention are in the range from about 0.2% to about 20% by weight and preferably about 2% to about 15% by weight. Alternatively the sweetener may be incorporated in one or all layers of multilayer film in varying amounts.

The surfactants generally comprise of one or more anionic surfactants ranging from about 1 % to about 5% by weight and preferably about 2% to about 4.5% by weight. Different surfactants that may be used in this invention include, without limitation, polysorbate 80, atoms 300, pluronic acid, sodium lauryl sulfate, polyoxyethylene sorbitan fatty acid ester or a polyoxyethylene castor oil derivative.

The plasticizers that may be used preparing multiple layer rapid dissolving film in the presently ^•*- described invention can vary, but generally selected from polyethylene glycol, propylene glycol, glycerin, polysorbates. Different grades of above mentioned plasticizer can be used singly or in y combination. The single layer rapid dissolving film may comprise one or more plasticizers ranging from about 0.5% to about 15% by weight and preferably about 1% to about 8.5% by weight.

Single or multiple numbers of antioxidants can be used for preparing multiple layer rapid dissolving film according to present invention. These antioxidants are well known in the art, which include water soluble and oil soluble antioxidants such as sodium sulphite, sodium metabisulfite, sodium bisulphite, sodium thiosulphate, sodium formaldehyde sulfoxylate, sulphur dioxide, ascorbic acid, gallic acid, propyl gallate, isoascorbic acid, thioglycerol, thioglycolic acid, cysteine hydrochloride, acetylcysteine, butylated hydroxy toluene, butylated hydroxy anisole, alpha tocopherols, lecithin, ascorbyl palmitate, propyl gallate, nordihydroguaiaretic acid. The antioxidants may be incorporated in single layer rapid dissolving film. Alternatively the antioxidants may be incorporated in one or all layers of multilayer film in varying amounts. The antioxidants are present in an amount ranging from about 0.1% to about 10% by weight and preferably at about 0.2% to about 5% by weight.

Single or multiple numbers of colouring agents can be used for preparing multiple layer rapid dissolving film according to present invention. These colouring agents are well known in the art, which include water soluble and oil soluble colours.

Single or multiple numbers of preservative can be used for preparing multiple layer rapid dissolving film according to present invention. These preservatives are well known in the art, which include water soluble and oil soluble preservatives such as benzoic acid, sorbic acid and its salts, propionic acid and its salt, chlorobutanol, methyl p-hydroxybenzoate, propyl p-hydroxy benzoate, benzyl p- hydroxybenzoate, butyl p- hydroxybenzoate, chlorhexidine and its salts, methyl parabens, propyl parabens. The preservatives may be incorporated in single layer and multilayer rapid dissolving film. Alternatively the preservatives may be incorporated in one or all layers of multilayer film in varying amounts. The preservative are present in the single or multilayer rapid dissolving film of the present invention in an amount ranging from about- 0.1% to about 5% by weight and preferably at about 0.2% to about 4% by weight.

In certain embodiments of the present invention are provided a single or multiple layer film having unique identification markings on the surface of the films, both artistic and informational markings can be produced. The informational marking placed on a film usually includes company name or symbol, product code, product name, potency of the product and the like.

In another embodiment of the present invention is provided a film with unique identification markings includes calendar wise or day wise prescription schedule printed or embossed on the film surface, which improves compliance of the patient with the medication. In another embodiment of the present invention a film with unique identification mark in the foπn of printed line printed or embossed on the film or film portions separated by perforations are provided for taking exactly Vi, 1/3 , 14 portion of film for taking exact dose as prescribed by the physician.

FIGURES AND LEGENDS

Figure. 1 is a perspective of single layer rapid dissolving film, Figure 1 a is a single layer film.

Figure 2, is a perspective of multilayer film, Figure (2a) depicts lateral view of multilayer film showing different layers in the multilayer film. Figure (2b) illustrates multilayer film differentiating individual film layer in a particular multilayer rapid dissolving film in which (a) is core (primary) film, (b) is inert exterior (secondary) film and (c) is exterior (secondary) film containing active.

Figure 3 is a perspective of printing unique identification markings en the single layer or multilayer film of different sizes and shapes incorporating different extracts in it. Figure 3a illustrated unique identification markings of name of a company or manufacturer or seller, which are illustrated in the figure in the form of name of company "UNIJULES" on the single layer or multilayer film of different sizes and shapes incorporating different extracts in it. The illustrated name "UNIJULES" may be replaced by any other name as desired. Figure 3b illustrates unique identification markings of a brand name, which is illustrated in the foπn of brand name of product "HERBOKAM" on the single layer or multilayer film of different sizes and shapes incorporating different extracts in it. This brand name may be replaced by relevant brand name as desired from case to case. Figure 3c illustrates unique identification markings in the form of dose of actives, which is illustrated by the mark "5mg" on the single layer or multilayer film of different sizes and shapes incorporating different extracts in it. This mark "5 mg" may be replaced by any other mark that is appropriate from case to case. Figure 3d, illustrates unique identification markings in the form of day on which dosage to be taken illustrated as "MONDAY" on the single layer or multilayer film of different sizes and shapes incorporating different extracts in it. This word "MONDAY" may be replaced by name of any other week day.

Figure 4 is a graphical presentation of Moisture Absorption study of thin film formulations.

Figure 5 is a graphical presentation of Study of tensile strength of thin film formulations.

Figure 6 Figure, is schematic representation of the process of making single layer edible film. Numbering depicted in it are the different steps and / or different parts of instruments are as follows :

1 - Mixing

2 - Debubbling 3 - Reservoir for slurry

4 - Pump to feed slurry in casting apparatus

5 - Slurry feeding tube

6 - Casting apparatus

7 - Roller 8 -Belt of substrate

9 - Casted wet film

10 - Drying zone (chambers)

1 1 - Dry thin edible film 12- Flash cooling zone 13 -Dried, cooled thin edible film at the end of casting line.

14 - Scrapper

15 - Scrapped film

16 - Roll of thin dissolving edible strips. is a schematic presentation Method of preparation of single layer film. Figure 7 is a Figures and legend in preparation of multiple layer film. Numbering depicted in it are the different steps and / or different parts of instruments are as follows :

1 - Mixing unit 1

2 - Debubbling unit 1

3 — Reservoir for slurry 1 4 - Pump to feed slurry in casting apparatus 1

5 - Slurry feeding tube 1

6 — Casting apparatus 1

7 - Roller 1&2 common

8 -Belt of substrate 1&2 common 9 — Casted wet single layer film

10 - Drying zone (chambers)

11 - Dry thin edible single layer film 12— Flash cooling zone

13 -Dried, cooled thin edible single layer film at the end of casting line. 14- Mixing unit II

15- Debubbling unit II 16- Reservoir for slurry II

17- Pump to feed slurry in casting apparatus II

18- Casting apparatus II

19- Casted wet multiple layer film 20 - Drying zone (chambers) II

21 - Dry thin edible multiple layer film 22- Flash cooling zone

23 -Dried, cooled thin edible single layer film at the end of casting line.

24 - Scrapper 25 — Scrapped multiple layer film

26 - Roll of thin dissolving multiple layer edible strips.

Different steps or processes described in the schematic representation can be performed in different manner. The mixing shown in figure can be performed in mixing vessel, colloidal mill and different mixing procedures known to the one skilled in the art. The debubbling can be performed under vacuum or ultrasonic waves or by the same methods generally used for debubbling. Alternatively any antifoaming agent can be incorporated in the film composition.

The suitable pumping systems selected from reciprocating, centrifugal or any other pumping- system, which does not adversely affect the film sluπy. Casting appaiatus (process) is selected- from spray coat method, comma blade method, doctor blade method, slot die coating and the like processes.

Casting substrate and casting line can be made of stainless steel, mylar or any other substrate that can be safely used for the manufacturing of pharmaceuticals.

Methods of Drying in the drying chambers (zones) are used are selected from amongst forced air, forced hot air, IR baffles from beneath the surface, combination of those and the same methods.

Cooling zones are adapted in the continuous line so as to cool the film along with substrate, this procedure reduces the recoiling of dry film after removal from the substrate at the end of casting line. The formed film can be removed at the end of casting line by the use of suitable scrapping

(scooping) assembly usually of cantilever or roll. The separated dry thin dissolving film is rolled to form a roll of thin edible film ready for cutting. Further the film is slit and further cut to form a single unit of thin edible film. Another embodiment of this invention for preparing multi layer rapid dissolving film of one or more than one herbal extracts (if they are needed to be physically separated) comprises herbal extract/ extracts, film forming materials, other adjutants and solvent. For preparing multilayer film, the core (primary) film comprising one or more than one herbal extracts is casted using method described above for single layer film. The core (primary) film is then dried and upon which several multiple layer of exterior (secondary) film are applied to lower or upper surface as required by the composition design. All the primary and secondary films are dried as mentioned earlier and the film is cut into dimensions as needed. The exterior (secondary) coats may be applied using any modern techniques of tape casting, alternatively the batch process of making films by pouring specified volume of slurry on the core (primary) film in specific area can be employed for producing multilayer rapid dissolving thin film foπnation. For producing thin wet film of exterior (secondary) film forming slurry on the core (primary) film, any of modern methods of tape casting using doctor blades, comma blade, microgravure coating, slot die conter. spray coating can be employed. Drying of the film may be carried out at high temperature using a drying oven, drying terminal, vacuum drier, forced air terminals or any other suitable drying equipment which does not adversely affect the ingredients of which the film is composed.

The multilayer rapid dissolving film once formed is cut in single consumable dosage units by die-cutting or slitting-and-die-cutting. The segmented film has a strip width and length generally about 10 to about 50 millimeters in width and about 20 to about 50 millimeters in length. Alternatively the multilayer rapid dissolving films may be cut into different sizes and shapes by using die of various shapes. The film has a thickness ranging from about 15 to about 120 micrometers, and preferably about 25 to 75 micrometers. The thickness of exterior (secondary) film may vary from 5 - 100 micrometers applied as single or more than one coat may or may not contain herbal extract/s on one or either side of the core (primary) film.

A process of making multiple layer rapid dissolving film products comprises selected steps as per requirement of product. a. Formation of slurry of all excipients and extracts/pharmaceutically active ingredients in aqueous or any suitable solvent.

b. Debubbling of formed slurry. Casting of slurry done by one of any methods selected from blade over belt method, spray cast method, slot die coating, comma blade process, pouring on substrate method.

c. Drying of casted wet film in the temperature 40- 70 ⁰C according to need of formulation.

d. Cooling of casting line along with dry film at the end of casting line, so as to reduce recoilin ^Λgo of film.

e. Gluing or casting over of inert or/ and active containing layer on primary film

f. Drying of multiple layer film

g. Cooling of casting line along with dry film at the end of casting line, so as to reduce recoiling of film.

h. Cutting and slitting of film strips in different size and shape to form a readily, unobtrusively consumable thin film formulation.

The process for application of wet slurry to releaseable belt is selected from spray coat method, comma blade method, doctor blade method, slot die coating and the like processes. Drying of wet films formed herein is achieved by any of processes selected from the group drying oven, drying terminal, vacuum drier, forced air terminals and the like. Drying of casted wet film in the temperature 40- 70 ⁰C according to need of formulation by drying oven, drying terminal, vacuum drier, forced air terminals and the like instruments. After complete drying of the film the films are cooled along with the substrate for reducing the recoiling of film. Cutting and slitting of film strips to form a readily, unobstrusively consumable thin film formulation. The present inventions also include, for example, without limitations, novel compositions of herbal extract/s with or without pharmaceutically active agent entrapped in single or multiple layer film for use as in various method of treatment of a mammal.

In the following are described experiments conducted that serve as non limiting illustrations of how the invention is performed. Any modifications or variations in the parameters including but not limited to process for extraction, formation of the film, are merely illustrative and any equivalents of them that are obvious to a person skilled in the art and capable of achieving the same objective may be used in their place and yet they shall be considered as included in the scope of this specification. Anything that is mentioned in singular in the specification also relates to its pleural unless h context does not permit so. Thus, "a polymer" shall also include use of another polymer having same function / properties as a replacement or in combination.

The following examples are given to illustrate working of the invention and the range of variables are not meant to limit the claims in any way, and any variation that shall be obvious for - a person skilled in the art from the description given here and the examples given below are considered to be included within the scope of the disclosure of the invention.

Example 1: PREPARATION OF SINGLE LAYER FILM

Example 1 a: PREPARATION OF SINGLE LAYER ANTIEMETIC FILM.

Materials taken per 1 kg batch of films (dry film weight)

Active substance and additives weight in grams Zingiber officinale Roxb. extract 100

Piper longum Linn, extract 100

Hydroxypropyl methyl cellulose 550

Kollicoat^®IR 100

Trehalose 55 Tween 80 15

Menthol 35

Clove oil 10 Aspartame 25 Bronopol 10

Sunset yellow (colour) 0.1 Water q. s. to 8 liters The volatile substances included in formula viz. Menthol and clove oil were mixed in separate batch process using over head stirrer, to this added the required amount of tween 80 as mentioned in the formula and mixed to form a dry (primary) emulsion. In a separate mixing process about 3 liters of water is taken to which added the above prepared dry (emulsion) composition and stirred for 15 minutes to form emulsion. To this emulsion added the filtered extract (filtered through musclien cloth) of Zingiber officinale Roxb., Piper longum Linn. Successively measured amounts of HPMC, Koliicoat IR, Trehalose G, Bronopol, sunset yellow are added and the liquid was stirred for 15 minutes. To this slurry added the required volume of water to produce slurry of 8 liters. The slurry was debubbled by keeping under vacuum for l_t0 minutes and the required quantity of slurry was poured on a glass substrate or casted by usin_j tape casting line to form a film of desired thickness. The film is dried in hot air oven, heating tunnel type of system with IR baffle, hot air blower, and after drying cut to a desired dimension, packaged and stored.

Example Ib: PREPARATION OF SINGLE LAYER MEMORY SUPPORT FILM. Materials taken per 1 kg batch of films (dry film weight)

Active substance and additives weight in grams

Bacopa monnieri Linn, extract 100

Centella asiatica Linn, extract 100 Hydroxypropyl methyl cellulose 550

Kollicoat^®IR 100

Trehalose 55

Tween 80 15

Menthol 35 Clove oil 10 Aspartame 25

Bronopol 10

Sunset yellow (colour) 0.5

Water q. s to 8 liters The volatile substances included in formula viz. Menthol and clove oil were mixed in separate batch process using over head stirrer, to this added the required amount of tween 80 as mentioned in the formula and mixed to form a dry (primary) emulsion. In a separate mixing process about 3 liters of water is taken to which added the above prepared dry (emulsion) composition and stirred for 15 minutes to form emulsion. To this emulsion added the filtered extract of (filtered through musclien cloth) of Bacopa monnieri Linn., Centella asiatica Linn. Successively measured amounts of HPMC, Koliicoat IR, Trehalose G, Bronopol, sunset yellow are added and the liquid was stirred for 15 minutes. To this slurry added the required volume of water to produce slurry of 8 liters. The slurry was debubbled by keeping under vacuum for 10 minutes and the required quantity of slurry was poured on a glass substrate or castcd by using tape casting line to form a film of desired thickness. The film is dried in hot air oven, heating tunnel type of system with IR baffle, hot air blower, and after drying cut to a desired dimension, packaged and stored.

Example Ic: PREPARATION OF SINGLE LAYER ANTIDIABETIC FILM. Materials taken per 1 kg batch of films (dry film weight)

Active substance and additives weight in grams

Momordica charantia Linn, extract 150

Hydroxypropyl methyl cellulose 550 Kollicoat^®IR 100

Trehalose 80

Tween 80 15

Menthol 35

Clove oil 10 Aspartame 50 Bronopol 10

Sunset yellow (colour) 0.1

Water q. s to 8 liters

The volatile substances included in formula viz. Menthol and clove oil were mixed in separate batch process using over head stirrer, to this added the required amount of tween 80 as mentioned in the formula and mixed to form a dry (primary) emulsion. In a separate mixing process about 3 liters of water is taken to which added the above prepared dry (emulsion) composition and stirred for 15 minutes to form emulsion. To this emulsion added the filtered extract (filtered through muslin cloth) of Momordica charantia Linn. Successively measured amounts of HPMC, Koliicoat IR, Trehalose G, Bronopol, sunset yellow are added and the liquid was stirred for 15 minutes. To this slurry added the required volume of water to produce slurry of 8 liters. The slurry was debubbled by keeping under vacuum for 10 minutes and the required quantity of slurry was poured on a glass substrate or casted by using tape casting line-to form a film of desired thickness. The film is dried in hot air oven, heating tunnel type of system with IR baffle, hot air blower, and after drying cut to a desired dimension, packaged and stored.

Example Id: PREPARATION OF SINGLE LAYER ANTIDIABETIC FILM.

Materials taken per 1 kg batch of films (dry film weight) Active substance and additives weight in grams

Azadirachta inclica A Juss. extract 150

Hydroxypropyl methyl cellulose 550

Kollicoat^®IR 100

Trehalose 80 Tween 80 15

Menthol 35

Clove oil 10

Aspartame 50

Bronopol 10 Sunset yellow (colour) 0.1

Water q. s to 8 liters The volatile substances included in formula viz. Menthol and clove oil were mixed in separate batch process using over head stirrer, to this added the required amount of tween 80 as mentioned in the formula and mixed to form a dry (primary) emulsion. In a separate mixing process about 3 liters of water is taken to which added the above prepared dry (emulsion) composition and stirred for 15 minutes to form emulsion. To this emulsion added the filtered extract (filtered through musclien cloth) of Azadirachta indica A Juss. Successively measured amounts of HPMC, Koliicoat IR, Trehalose G, Bronopol, sunset yellow are added and the liquid was stirred for 15 minutes. To this slurry added the required volume of water to produce slurry of 8 liters. The slurry was debubbled by keeping under vacuum for 10 minutes and the required quantity of slurry was poured on a glass substrate or casted by using tape casting line to foπn a film of desired thickness. The film is dried in hot air oven, heating tunnel type of system with IR baffle, hot air blower, and after drying cut to a desired dimension, packaged and stored.

Example Ie: PREPARATION OF SINGLE LAYER ANTISTRESS FILM.

Materials taken per 1 kg batch of films (dry film weight)

Active substance and additives weight in grams

Withania somnifera Dunal. extract 60

Bacυpa monnieri Linn, extract 90 Nardυstachys jatamansi DC extract 50

Hydroxypropyl methyl cellulose 550

Kollicoat^®IR 100

Trehalose . 55

Tween 80 15 Menthol 35

Clove oil 10

Aspartame 25

Bronopol 10

Sunset yellow (colour) 0.1 Water q. s to 8 liters The volatile substances included in formula viz. Menthol and clove oil were mixed in separate batch process using over head stirrer, to this added the required amount of tvveen 80 as mentioned in the formula and mixed to form a dry (primary) emulsion. In a separate mixing process about 3 liters of water is taken to which added the above prepared dry (emulsion) composition and stirred for 15 minutes to form emulsion. To this emulsion added the filtered extract (filtered through musclien cloth) of Withania somnifera Dunal., Bacopa monnieri Linn., Nardostachys jatamansi DC extract. Successively measured amounts of HPMC, Koliicoat IR, Trehalose G, Bronopol, sunset yellow are added and the liquid was stirred for 15 minutes. To this slurry added the required volume of water to produce slurry of 8 liters. The slurry was debubbled by keeping under vacuum for 10 minutes and the required quantity of slurry was poured on a glass substrate or casted by using tape casting line to form a film of desired thickness. The film is dried in hot air oven, heating tunnel type of system with IR baffle, hot air , blower, and after drying cut to a desired dimension, packaged and stored.

Example If: PREPARATION OF SINGLE LAYER DIURETIC FILM.

Materials taken per 1 kg batch of films (dry film weight)

Active substance and additives weight in grams

Boerhavia diffusa Linn, extract 100

Tribulus terrestris Linn, extract 100 Hydroxypropyl methyl cellulose 550

Kollicoat^®IR 100

Trehalose 55

Tween 80 15

Menthol 35 Clove oil 10

Aspartame 25

Bronopol 10

Sunset yellow (colour) 0.1

Water q. s. to 8 liters The volatile substances included in formula viz. Menthol and clove oil were mixed in separate batch process using over head stirrer, to this added the required amount of tween 80 as mentioned in the formula and mixed to form a dry (primary) emulsion. In a separate mixing process about 3 liters of water is taken to which added the above prepared dry (emulsion) composition and stirred for 15 minutes to form emulsion. To this emulsion added the filtered extract (filtered through musclien cloth) of Boerhavia diffusa Linn, Tribulus terrestήs Linn. Successively measured amounts of HPMC, Koliicoat IR, Trehalose G, Bronopol, sunset yellow are added and the liquid was stirred for 15 minutes. To this slurry added the required volume of water to produce slurry of 8 liters. The slurry was debubbled by keeping under vacuum for 10 minutes and the required quantity of slurry was poured on a glass substrate or casted by using tape casting line to form a film of desired thickness. The film is dried in hot air oven, heating tunnel type of system with IR baffle, hot air blower, and after drying cut to a desired dimension, packaged and stored.

Example Ig: PREPARATION OF SINGLE LAYER HEPATOPROTECTIVE FILM.

Materials taken per 1 kg batch of films (dry film weight)

Active substance and additives weight in grams

Picrorhiza kurroa Royle ex Benth. extract 70 Phyllanthus niruri Linn, extract 130

Hydroxypropyl methyl cellulose 550

Kollicoat^®IR 100

Trehalose 55

Tween 80 15 Menthol 35

Clove oil 10

Aspartame 25

Bronopol 10

Sunset yellow (colour) 0, 1 Water q. s to 8 liters The volatile substances included in formula viz. Menthol and clove oil were mixed in separate batch process using over head stirrer, to this added the required amount of tween 80 as mentioned in the formula and mixed to form a dry (primary) emulsion. In a separate mixing process about 3 liters of water is taken to which added the above prepared dry (emulsion) composition and stirred for 15 minutes to form emulsion. To this emulsion added the filtered extract (filtered through musclien cloth) of Picrorhiza kurroa Royle ex Benth., Phyllanthus niniri Linn.. Successively measured amounts of HPMC, Koliicoat IR, Trehalose G, Bronopol, sunset yellow are added and the liquid was stirred for 15 minutes. To this slurry added the required volume of water to produce slurry of 8 liters. The slurry was debubbled by keeping under vacuum for 10 minutes and the required quantity of slurry was poured on a glass substrate or casted by using tape casting line to form a film of desired thickness. The film is dried in hot air oven, heating tunnel type of system with IR baffle, hot air blower, and after drying cut to a desired dimension, packaged and stored.

Example Ih: PREPARATION OF SINGLE LAYER ANTIDIARRHEAL FILM.

Materials taken per 1 kg batch of films (dry film weight)

Active substance and additives weight in grams

Holarrhena antidysentrica (Roth) A. DC. extract 150 Euprhorbia hirta Linn, extract 50

Hydroxypropyl methyl cellulose 550

Kollicoat^®IR 100

Trehalose 55

Tween 80 15 Menthol 35

Clove oil 10

Aspartame 25

Bronopol 10

Sunset yellow (colour) 0.1 Water q. s to 8 liters The volatile substances included in formula viz. Menthol and clove oil were mixed in separate batch process using over head stirrer, to this added the required amount of tween 80 as mentioned in the formula and mixed to form a dry (primary) emulsion. In a separate mixing process about 3 liters of water is taken to which added the above prepared dry (emulsion) composition and stirred for 15 minutes to form emulsion. To this emulsion added the filtered extract (filtered through musclien cloth) of Holarrhena antidysentrica (Roth) A. DC, Euprhorbia hirta Linn. Successively measured amounts of HPMC, Koliicoat IR, Trehalose G, Bronopol, sunset yellow are added and the liquid was stirred for 15 minutes. To this slurry added the required volume of water to produce slurry of 8 liters. The slurry was debubbled by keeping under vacuum for 10 minutes and the required quantity of slurry was poured on a glass substrate or casted by using tape casting line to form a film of desired thickness. The film is dried in hot air oven, heating tunnel type of system with IR baffle, hot air blower, and after drying cut to a desired dimension, packaged and stored.

Example Ii: PREPARATION OF SINGLE LAYER GALACTOGOGUE FILM.

Materials taken per 1 kg batch of films (dry film weight)

Active substance and additives weight in grams

Asparagus racemosus Willd. extract 70 Euphorbia hitra Linn, extract 25

Pueraria tuberose DC. extract 40

Trigonella foenum- graceum Linn. Extract 40

Leptadenia raticulata wight and Am. Extract 30

Withania somnifera Dunal. Extract 20 Hydroxypropyl methyl cellulose 525

Kollicoat^®IR 100

Trehalose 55

Tween 80 15

Menthol 35 Clove oil 10 Aspartame 25

Bronopol 10

Sunset yellow (colour) 0.1

Water q. s. to 8 liters

The volatile substances included in formula viz. Menthol and clove oil were mixed in separate batch process using over head stirrer, to this added the required amount of tween 80 as mentioned in the formula and mixed to form a dty (primary) emulsion. In a separate mixing process about 3 liters of water is taken to which added the above prepared dry (emulsion) composition and stirred for 15 minutes to form emulsion. To this emulsion added the filtered extract (filtered through musclien cloth) of Asparagus racemosiis WHId., Euphorbia hitra Linn., Pueraria tuberose DC, Trigonella foeni.'m- gracewn Linn., Leptadenia reticulata wight and Am. and Withania somnifera Duncil. Successively measured amounts of HPMC. Koliicoat IR, Trehalose G, Bronopol, sunset yellow jre added and the liquid was stared for 15

this slurry added the required volume of water to produce slurry of 8 liters. The slurry was debubbled by keeping under vacuum for 10 minutes and the required quantity of slurry was poured on a glass substrate or casted by using tape casting line to form a film of desired thickness. The film is dried in hot air oven, heating tunnel type of system with IR baffle, hot air blower, and after drying cut to a desired dimension, packaged and stored.

Example Ij: PREPARATION OF SINGLE LAYER CARDIOTONIC FlLIVl.

Materials taken per 1 kg batch of films (dry film weight)

Active substance and additives weight in grams Tribuliis terrestris Linn, extract 70

Terminalia arjuna W and A. extract 130

Pueraria tuberose DC. extract 40

Trigonella foenum- gracewn Linn. Extract 40

Leptadenia raticulata wight and Am. Extract 30 Withania somnifera Dunal. Extract 20

^O Hydroxypropyl methyl cellulose 525

Kollicoat^®IR 100

Trehalose 55

Tween δO 15 Menthol 35

Clove oil 10

Aspartame 25

Bronopol 10

Sunset yellow (colour) 0.1 Water q. s. to 8 liters

The volatile substances included in formula viz. Menthol and clove oil were mixed in separate batch process using over head stirrer, to this added the required amount of tween 80 as mentioned in the formula and mixed to foπn a dry (primary) emulsion. In a separate mixing process about 3 liters of water is taken to which added the above prepared dry (emulsion) composition and stirred for 15 minutes to foπn emulsion. To this emulsion added the filtered % extract (filtered through musclien cloth) of Tribulus terrestris Linn, and Terminalia arjuna W and A.. Successively measured amounts of HPMC, Koliicoat IR, Trehalose G, Bronopol, sunset yellow are added and the liquid was stirred for 15 minutes. To this slurry added the required volume of water to produce slurry of 8 liters. The slurry was debubbled by keeping under vacuum for 10 minutes and the required quantity of slurry was poured on a glass substrate or casted by using tape casting line to form a film of desired thickness. The film is dried in hot air oven, heating tunnel type of system with IR baffle, hot air blower, and after drying cut to a desired dimension, packaged and stored. Example 2: PREPARATION OF MULTIPLE LAYER FILM BY GLUING METHOD

For preparing fast dissolving multiple layer film by gluing method different extract are casted and formed individual basic film. These basic films are then glued to form a multiple layer dissolvable film. Thus the preparation involves process of forming basic films of different herbal extract followed by gluing them together. Example 2a: PREPARATION OF MULTILAYER ANTIEMETIC FILM. A. Preparation of basic films

Different basic films of Zingiber officinale Roxb. Extract and Piper longum Linn, extract was prepared according to following formulas.

Materials taken per 1 kg batch of films (dry film weight)

Active substance and additives weight in grams

Zingiber officinale Roxb. extract 200

Hydroxypropyl methyl cellulose 550 Kollicoat^®IR 100

Trehalose 55

Tween 80 15

Menthol 35

Clove oil 10 Aspartame 25

Bronopol 10

Sunset yellow (colour) 0.1

Water q. s to 8 liters

The volatile substances included in formula viz. Menthol and clove oil were mixed in separate batch process using over head stirrer, to this added the required amount of tween 80 as mentioned in the formula and mixed to form a dry (primary) emulsion. In a separate mixing process about 3 liters of water is taken to which added the above prepared dry (emulsion) composition and stirred for 15 minutes to form emulsion. To this emulsion added the filtered extract (filtered through musclien cloth) of Zingiber officinale Roxb. Successively measured amounts of HPMC, Koliicoat IR, Trehalose G, Bronopol, sunset yellow are added and the liquid was stirred for 15 minutes. To this slurry added the required volume of water to produce slurry of 8 liters. The slurry was debubbled by keeping under vacuum for 10 minutes and the required quantity of slurry was poured on a glass substrate or casted by using tape casting line to form a film of desired thickness. The film is dried in hot air oven, heating tunnel type of system with IR baffle, hot air blower, and after drying cut to a desired dimension, packaged and stored.

Preparation of basic films of Piper Ionium Linn, extract

Materials taken per 1 kg batch of films (dry film weight)

Active substance and additives weight in grams

Piper longum Linn, extract 200 Hydroxypropyl methyl cellulose 550

Kollicoat^®lR 100

Trehalose 55

T ween 80 15

Menthol 35 Clove oil 10

Aspartame 25

Bronopol 10

Sunset yellow (colour) 0.1

Water q. s to 8 liters

The volatile substances included in formula viz. Menthol and clove oil were mixed in separate batch process using over head stirrer, to this added the required amount of tween 80 as mentioned in the formula and mixed to form a dry (primary) emulsion. In a separate mixing process about 3 liters of water is taken to which added the above prepared dry (emulsion) composition and stirred for 15 minutes to form emulsion. To this emulsion added the filtered extract (filtered through musclien cloth) of Piper longum Linn. Successively measured amounts of HPMC, Kollicoat^® IR, Trehalose G, Bronopol, sunset yellow are added and the liquid was stirred for 15 minutes. To this slurry added the required volume of water to produce slurry of 8 liters. The slurry was debubbled by keeping under vacuum for 10 minutes and the required quantity of slurry was poured on a glass substrate or casted by using tape casting line to form a film of desired thickness. The film is dried in hot air oven, heating tunnel type of system with IR baffle, hot air blower, and after drying cut to a desired dimension, packaged and stored. B. Gluing of basic films

Different basic films of Zingiber officinale Roxb. Extract and Piper longum Linn. Extract were prepared accordingly, and are glued by using polymeric gluing solution. The gluing solution can be applied by spraying or spreading over blade method. The individual formed basic films are then passed through roller compactor and subsequently dried to form a multilayer film. Composition of gluing solution.

Materials taken per 1 liter batch of polymeric gluing solution

Additives weight in grams

Polyoxyethylene 25

Butylated hydroxy toluene 0.25 gm Ethanol q. s to 1 liter

Example 3: PREPARATION OF MULTI LAYER FILM BY CAST OVER FILM METHOD

For preparing fast dissolving multilayer film by cast over primary film method different pharmaceutically active ingredient / pharmaceutically active ingredients are casted in the form of core (primary) film and over this core film, subsequently different layers of exterior(secondary)films are formed. Optionally an inert layer comprising no pharmaceutically active ingredients can be applied between two layers of pharmaceutically active ingredients. This method is differentiated from the above described gluing method that, in the gluing method individual films containing different pharmaceutically active ingredients are formed separately and then fused (glued) together. In cast over film method the different casting slurry of different pharmaceutically active ingredients is applied successively on the core film. Example 3a: PREPARATION OF MULTI LAYER ANTIEMETIC FILM BY CAST OVER FILM METHOD

Preparation of Core (Primary) film

The core film of any individual herb or combination of noninteracting extracts can be prepared by the same method as described in basic film preparation process. This basic film was then coated with the exterior (secondary) film forming slurry containing different extract/combination of extracts as needed according to formulation. Core (primary) films containing Zingiber officinale Roxb. extract was prepared according to following formulas

Preparation of Core (Primary) film of Zingiber officinale Roxb. Extract

Materials taken per 1 kg batch of films (dry film weight)

Active substance and additives weight in grams Zingiber officinale Roxb. extract 200

Hydroxypropyl methyl cellulose 550

Kollicoat^®IR 100

Trehalose 55

Tween 80 15 Menthol 35

Clove oil 10

Aspartame 25

Bronopol 10

Sunset yellow (colour) 0.1 Water q. s to 8 liters

Application of additional (secondary^*) film of Piper longum Linn, extract

Materials taken per 1 liter batch of secondary film forming slurry of Piper longum Linn. Extract.

Active substance and additives weight in grams

Piper longum Linn, extract 20

Hydroxypropyl methyl cellulose 1 Polyoxyethylene 50

Butylated hydroxy toluene 0.1

Tween 80 2

Menthol 2

Clove oil 2 Aspartame 5

Bronopol 0.5

Sunset yellow (colour) 0.1

Ethanol q. s to 1 liter

The volatile substances included in formula viz. Menthol and clove oil were mixed in separate batch process using over head stirrer, to this added the required amount of tween 80 as mentioned in the formula and mixed to form a dry (primary) emulsion. In a separate mixing process, 0.5 liter of ethanol is taken to which added the above prepared dry (emulsion) composition and stirred for 15 minutes to form emulsion. To this composition added the filtered extract (filtered through muslin cloth) of Piper longum Linn, Successively measured amounts of HPMC, Bronopol, sunset yellow and other adjutants are added and the liquid was wanned and stirred for 15 minutes. To this warm slurry added the required volume of ethanol (absolute) to produce slurry of 1 liter. The slurry was debubbled by keeping under vacuum for 10 minutes and the required quantity of slurry was poured on core (primary) film or casted upon core (primary) film by using tape casting line to form a exterior (secondary) film of desired thickness. The film is dried in hot air oven, heating tunnel type of system with IR baffle, hot air blower, and after drying multilayer film cut to a desired dimension, packaged and stored.

Example 4: PREPARATION OF MULTILAYER ANTICOLD FILM OF NON-HERBAL PHARMACEUTICAL ACTIVES.

Example 4a: PREPARATION OF MULTILAYER ANTICOLD FILM OF NON- HERBAL PHARMACEUTICAL ACTIVES BY GLUING.

Preparation of basic films

Different basic films of chlorpheniramine maleate and phenylephrine were prepared according to * following formulas.

Preparation of basic films of chlorpheniramine maleate

Materials taken per 1 kg batch of films (dry film weight)

Active substance and additives weight in grams

Chlorpheniramine maleate 200 Hydroxypropyl methyl cellulose 550

Kollicoat^®IR 100

Trehalose 55

Tween 80 15

Menthol 35 Clove oil 10

Aspartame 25

Bronopol 10

Sunset yellow (colour) 0.1

Water q. s. to 8 liters The volatile substances included in formula viz. Menthol and clove oil were mixed in separate batch process using over head stirrer, to this added the required amount of tween 80 as mentioned in the formula and mixed to form a dry (primary) emulsion. In a separate mixing process about 3 liters of water is taken to which is added the above prepared dry (emulsion) composition and stirred for 15 minutes to form emulsion. To this emulsion is added the chlorpheniramine maleate. Successively measured amounts of HPMC, Kollicoat IR, Trehalose G, Bronopol, sunset yellow are added and the liquid was stirred for 15 minutes. To this slurry added the required volume of water to produce slurry of 8 liters. The slurry was debubbled by keeping under vacuum for 10 minutes and the required quantity of slurry was poured on a glass substrate or casted by using tape casting line to form a film of desired thickness. The film is dried in hot air oven, heating tunnel type of system with IR baffle, hot air blower, and after drying cut to a desired dimension, packaged and stored.

Preparation of basic films of Phenylephrine

Materials taken per 1 kg batch of films (dry film weight)

Active substance and additives weight in grams Phenylephrine 150

Hydroxypropyl methyl cellulose 550

Kollicoat^®IR 100

Trehalose 55

Tween 80 15 Menthol 35

Clove oil 10

Aspartame 25

Bronopol 10

Sunset yellow (colour) 0.1 Water q. s to 8 liters The volatile substances included in formula viz. Menthol and clove oil were mixed in separate batch process using over head stirrer, to this added the required amount of tween 80 as mentioned in the formula and mixed to form a dry (primary) emulsion. In a separate mixing process about 3 liters of water is taken to which added the above prepared dry (emulsion) composition and stirred for 15 minutes to form emulsion. To this emulsion added the fine powdered Phenylephrine. Successively measured amounts of HPMC, Koliicoat IR, Trehalose G, Bronopol, sunset yellow are added and the liquid was stirred for 15 minutes. To this slurry added the required volume of water to produce slurry of 8 liters. The slurry was debubbled by keeping under vacuum for 10 minutes and the required quantity of slurry was poured on a glass substrate or casted by using tape casting line to form a film of desired thickness. The film is dried in hot air oven, heating tunnel type of system with IR baffle, hot air blower, and after drying cut to a desired dimension, packaged and stored.

Gluing of basic films

Different basic films of chlorpheniramine maleate and phenylephrine were prepared accordingly, and are glued by using polymeric gluing solution. The gluing solution can be applied by spraying or spreading over blade method. The individual formed basic films are then passed through roller compactor and subsequently dried to form a multilayer film.

Composition of gluing solution.

Materials taken per 1 liter batch of polymeric gluing solution

Additives weight in grams

Polyoxyethylene 25

Butylated hydroxy toluene 0.25 gm

Ethanol q. s to 1 liter

Example 4b: PREPARATION OF MULTILAYER ANTICOLD FILM OF NON- HERBAL PHARMACEUTICAL ACTIVES BY CAST OVER FILM METHOD For preparing fast dissolving multilayer film by cast over primary film method different extract/extracts are casted in the form of core (primary) film and over this core film, subsequently different layers of additional (secondary) films are formed. Optionally an inert layer without comprising any extract can be applied between two layers of extract. This method is differentiated from the above described gluing method in that, in the gluing method individual films containing different extracts are formed separately and then fused (glued) together. In cast over film method the different casting slurry of different extracts are applied successively on the core film.

Preparation of Core (Primary) film

The core film of any individual or combination of noninteracting pharmaceutically active ingredients can be prepared by the same method as described in basic film preparation process. This basic film was then coated with the additional (secondary) film forming slurry containing different single / combination of pharmaceutically active ingredients as needed according to foπnulation. Core (primary) films containing chlorpheniramine maleate was prepared according to following formulas

Preparation of Core (Primary) film of chlorpheniramine maleate

Materials taken per 1 kg batch of films (dry film weight)

Active substance and additives weight in grams

Chlorpheniramine maleate 200

Hydroxypropyl methyl cellulose 550

Kollicoat^®IR 100

Trehalose 55 Tween 80 15

Menthol 35

Clove oil 10

Aspartame 25

Bronopol 10 Sunset yellow (colour) 0.1

Water q. s to 8 liters

The volatile substances included in formula viz. Menthol and clove oil were mixed in separate batch process using over head stirrer, to this added the required amount of tween 80 as mentioned in the formula and mixed to form a dry (primary) emulsion. In a separate mixing process about 3 liters of water is taken to which added the above prepared dry (emulsion) composition and stirred for 15 minutes to form emulsion. To this emulsion added the fine powder of chlorpheniramine maleate. Successively measured amounts of HPMC, Koliicoat IR, Trehalose G, Bronopol, sunset yellow are added and the liquid was stirred for 15 minutes. To this slurry added the required volume of water to produce slurry of 8 liters. The slurry was . debubbled by keeping under vacuum for 10 minutes and the required quantity of slurry was ■ poured on a glass substrate or casted by using tape casting line to form a film of desired.*;,, thickness. The film is dried in hot air oven, heating tunnel type of system with IR baffle, hot air . = blower, and after drying cut to a desired dimension, packaged and stored.

Application of additional (secondary^*) film of Phenylephrine

Materials taken per 1 liter batch of additional (secondary) film forming slurry of Piper lυngum Linn. Extract.

Active substance and additives weight in grams Phenylephrine 20

Hydroxypropyl methyl cellulose 1

Polyoxyethylene 50

Butylated hydroxy toluene 0.1

Tween 80 2 Menthol 2

Clove oil 2

Aspartame 5

Bronopol 0.5 Sunset yellow (colour) 0.1

Ethanol q. s to 1 liter

The volatile substances included in formula viz. Menthol and clove oil were mixed in separate batch process using over head stirrer, to this added the required amount of tween 80 as mentioned in the formula and mixed to form a dry (primary) emulsion. In a separate mixing process, 0.5 liter of ethanol is taken to which added the above prepared dry (emulsion) composition and stirred for 15 minutes to form emulsion. To this composition added the fine powder of phenylephrine. Successively measured amounts of HPMC, Bronopol, sunset yellow and other adjutants are added and the liquid was warmed and stirred for 15 minutes. To this warm slurry added the required volume of ethanol (absolute) to produce slurry of 1 liter. The slurry was debubbled by keeping under vacuum for 10 minutes and the required quantity of slurry was poured on core (primary) film or casted upon core (primary) film by using tape casting line to form a exterior (secondary) film of desired thickness. The film is dried in hot air oven, heating tunnel type of system with IR baffle, hot air blower, and after drying multilayer film cut to a desired dimension, packaged and stored.

Example 5: Stability study

The stability is essential in any product that reaches the market. The stability study of the present pullulan free rapid (fast) dissolving films was performed according to guidelines of International Conference on Harmonization (ICH). Apart from these guidelines some characteristic study which are important for assessing film property were also performed. Herein is given the data of four different batches. The batch comprised of two single layer rapid dissolving film as described in Example Ia and Ic, a multilayer film prepared by gluing method as described in example 2a and one Example which uses cast over film method as described in Example 3a. Thus all the processes were assessed accordingly. Thus all the processes were assessed accordingly According to ICH guidelines, studies were performed for 6 months at 75 % RH. Different parameters were analyzed for assessing the stability of different film formulations prepared by various above-mentioned processes. The parameters assessed are opacity of film, appearance of film, tensile strength of film, folding endurance of film formulation, moisture absorption study. The description of study is given below

A. Assessing stability of film formulation.

For assessing stability of film formulations, different film formulations prepared by various methods were prepared. Different physical characteristics of films were assessed at day one and after keeping the same formulations at accelerated stability conditions. Shown in the figure 5 is the comparison of tensile strength of same film formulation batch (Example Ia, Ic, 2a, 3a) on the day of production and after six months accelerated stability study. Shown in the Table 1 and Table 2 is the comparison of folding endurance, tensile strength, self adherence and dissolving time of same film formulation batch (Example Ia, Ic, 2a, 3a) on the day of production (Table 1) and after six months accelerated stability study (Table 2). No significance difference was observed in the physical and film properties of all formulations.

Table 1

„ . .. Tensile Dissolving

Formulation Folding . ,. Self

, strength time (in code endurance _(N/m^₂₎ adherence seconds)

Example Ia 7 6.2136 No 30

Example Ic 7 6.6823 No 30

Example 2a 8 7.8945 No 40

Example 3a 9 8.4589 No 45 Table 2

„ . .. Tensile Dissolving

Formulation Folding . .. Self

, strength time (in code endurance _(N/m^₂₎ adherence seconds)

Example Ia 6 6.1562 No 30

Example Ic 5 6.1838 No 25

Example 2a 7 7.2967 No 35

Example 3a 8 8.4367 No 40

B. Assessment of Water (moisture) resistance character of film formulation.

Also the study was conducted for assessing water resistance (sustenance) of film formulation. Table 3 explains the moisture absorption at different humidity conditions after 6 days of exposure; no significant water (moisture) absorption was evident from study. This parameter explains the water (humidity) sustenance of the film formulation disclosed in the present invention.

Table 3 Formulation Code % Moisture absorption at different % R.H.

23 % 43 % 75 % 93 %

Example Ia 2.84 3.14 3.89 5.34

Example Ic 2.97 3.38 4.22 5.64

Example 2a 3.16 3.91 4.80 5.88

Example 3a 3.61 4.76 4.92 5.78

Claims

1. An oral film for delivering an active ingredients to oral cavity, wherein the said oral film requires at least a delay of about 5 seconds after coming in contact with oral mucosa to stick to the mucosa surface in contact and rapidly dissolves thereafter.

2. An oral film of claim 1 further comprising the said active ingredient as a herbal or a non-herbal.

3. An oral film of claim 2 comprising a single layer film or a multilayer film.

4. An oral film of claim 3 comprising a polyvinyl alcohol polyethylene glycol graft polymer having low viscosity and a cellulose derivative as film foπning polymers and additives.

5. An oral film of claim 4 wherein the said additives comprise an additional one more water soluble polymer, a surfactant, a stabilizing agent, an emulsifier, a plasticizer, a water soluble sugar, a binder, a sweetener, a flavors, a plasticizer, an antioxidant, a volatile oil and combinations thereof.

6. An oral film of claim 5 wherein:

a. polyvinyl alcohol polyethylene glycol graft polymer, is present in the film composition to the extent of between 5% and 50%, more preferably 5% - 40% by weight of the film composition, and/or

b. the said other water soluble polymer present in the film formulation in combination with graft polymer are selected from group consisting of, hydroxypropyl methyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, carboxy methyl cellulose, guar gum, carboxy methyl guar gum, carboxy methyl locust bean gum, acacia gum, arabic gum, pectin, chitosan, mixtures thereof and the like polymers to the extent of between 10% and 50% by weight of the film composition, and/or

c. the said polyvinyl alcohol polyethylene glycol graft polymer has a viscosity in the range of 130 to 190 millipascal seconds, when viscosity of a 20 % solution is found at 23 °C , more preferably 150 to 170 millipascal seconds when viscosity of a 20 % solution is found at 23°C, and/or

d. the said water soluble sugar is selected from the group consisting of glucose, dextrose, fructose, lactose, maltose, xylose, sucrose, trehalose G and the like, combinations thereof to the extent of between 1% and 10%; more preferably the high water soluble sugar used is trehalose G to the extent 1% - 10% or more preferably to the extent of 2% - 8% by weight of the film composition, and/or

e. the said sweetener is selected from the group consisting of synthetic sweeteners and natural sweeteners such as sorbitol, hexitol, Maltitol, xylitol, mannitol, aspartame, saccharine sodium, sucralfate, alitame, cyclamate, acesulfame and the like; in an amount ranging from about 0.2% to about 20% by weight and preferably about 2% to about 15% by weight, and further used singly or in a combination of sweeteners preferably selected from the group consisting of synthetic sweeteners and sugar-related compound in an amount ranging from about 0.2% to about

20% by weight and preferably about 2% to about 15% by weight of the film composition, and/or

f. the said antioxidant is selected from two categories, which include water soluble and oil soluble antioxidants such as sodium sulphite, sodium metabisulfite, sodium bisulphite, sodium thiosulphate, sodium formaldehyde sulfoxylate, sulphur dioxide, ascorbic acid, gallic acid, propyl gallate, isoascorbic acid, thioglycerol, thioglycolic acid, cysteine hydrochloride, acetylcysteine, butylated hydroxy toluene, butylated hydroxy anisole, alpha tocopherols, lecithin, ascorbyl palmitate, propyl gallate, nordihydroguaiaretic acid, and the like. The antioxidants may be incorporated in single layer rapid dissolving film. The antioxidants are present in the single layer rapid dissolving film of the present invention in an amount ranging from about 0.1% to about 10% by weight and preferably about 0.2% to about 5% by weight of the film composition, and/or

g. the said surfactant is selected from polyethylene glycol, propylene glycol, glycerin, polysorbates, used singly or in combination in a range of about 0.5% to about 15% by weight and preferably about 1% to about 8.5% by weight of the film composition, and/or

h. the said volatile oil is selected from the group consisting of lemon oil, orange oil, lemon grass oil, cinnamon oil, clove oil, ginger oil, spearmint oil, peppermint oil, eucalyptus oil, oil of nutmeg, mentha piperita (menthol), to the extent between 0.1% and 5%; or an isolated volatile oil fractions selected from the group consisting of eugenol, fenchone, anethol, gingerol, shagoal, pipeline, methyl salicylate and the like fractionated isolated volatile oil fractions to the extent between 0.1% and 5% by weight of the film composition, and/or

i. the said surfactant is selected from the group polysorbate 80, atoms 300, pluronic acid, sodium lauryl sulphate, polyoxyethylene sorbitan fatty acid ester or a polyoxyethylene castor oil derivatives to the extent between 1 to 5%, more preferably to 2 to 4 % by weight of the film composition, and/or,

j. the said stabilizing agent is selected from the group xanthan gum, locust bean gum, carrageenan, guar gum and mixtures thereof to the extent between 1 to 5%, more preferably to 1 to 3 % by weight of the film composition, and/or,

k. the said emulsifier is selected from the group lecithin, stearates, non ionic surfactants, synthetic waxes, polyoxyethylene alkyl ethers, or polyoxyethylene castor oil to the extent between 1 to 5 %, more preferably between 2 to 3 % by weight of the film composition, and/or,

1. the said plasticizer is selected from the group polyethylene glycol, N propylene glycol, glycerin, polysorbates to the extent between 0.5 to 15 %, more preferably between 1 to 8.5 % by weight of the film composition, and/or,

m. the said binder is polyoxyethylene to the extent between 0.5 to 3 % more preferably between 0.5 to 2% by weight of the film composition, and/or,

n. the said flavor is selected from the group lemon oil, orange oil, lemon grass oil, cinnamon oil, clove oil, ginger oil, spearmint oil, peppeπnint oil, eucalyptus oil, oil of nutmeg, Mentha piperita (menthol), methyl salicylate , peppeπnint, vanilla to the extent between 0.1 to 10, more preferably between 0.4 to 5 % by weight of the film composition.

7. An oral film of claim 6 comprising at least one herbal or non-herbal active ingredient and (a) in a single file additional ingredients comprising

Hydroxypropyl methyl cellulose, Kollicoat^®IR, Trehalose, Tween 80, Menthol, Clove oil, Aspartame, Bronopol and Sunset yellow (colour), and (b) further additional ingredients comprising polyoxyethylene and Butylated hydroxyl toluene in a multilayer film.

8. An oral film of claim 6 wherein the herbal extract ingredient is prepared from a botanical part of the plant.

9. An oral film of claim 8 wherein the said botanical part of a plant comprises at least whole or part of a root, a stem, a bark, a leaf, a flower, a fruit, a seed or whole plant.

10. An oral film of claim 9 wherein the said extraction process comprises at least one from group of processes comprising cold extraction technique, soxhlet extractor, making a decoction, supercritical extraction, microwave extraction using a variety of different extraction solvents.

1 1. An oral film of claim 10 wherein the said solvents include a solvent selected, from the group ethanol, methanol, acetone, acetonitrile, chloroform, water, hydroalcoholic mixture and isopropyl alcohol.

12. An oral film of claim 11, wherein the said herbal ingredient is selected from a group of plants comprising Zingiber officinale Roxb., Piper longum Linn., Boswellian serrata Roxb., Vitex negunda Linn., Tinospora codifolia, Curcuma longa Linn., Centella asiatica Linn., Bacopci monnieri Linn., Momordica charantia Linn., Azadirachta indica, Ocimum sanctum, Picrorhiza kurroa Royle ex benth, Withania somnifera, Tribulus terristris Linn., Nardostachys jatamansi,

Boerhavia diffusa Linn., Phyllanthus niruri Linn., Cassia angustifolia Vahl., Holarrhena antidysentrica (Roth), Asparagus racemosus Willd., Allivum sativum Linn., Euphorbia hirta Linn., Peuraria tuberosa., Leptadia reticulata, Trigonella foenum-graceum Linn., Mucuna prureins Baker., Terminalia arjuna, Achyranthes bidentatae Wall, Achyranthes aspera Linn, Achyranthes prophyristachya Wall, Aconitum napellus Linn, Aconis americanus, Actinidia arguta, Aclinidia arguta, Actinidia arisanensis, actinidia eallosa, Adenophora tetraphylla Radix, Albizia julibrissin, Alisma caniculatum, Alisma orientale, Alpinia magnifera Rose, Alpenia galangal Willd, panax quinquefolium Linn, Asparagusracemosus Willd, Astragalus membranaceus, Atractylodesmacrocephalae, Biota orientalis Semen,

Bupleurum Chinese Radix, Chrysanthemum morifolium Flos, chrysanthemum indicum Flos, Cibotium barometz, cnidium monnieri, codonopsis pilosula Radix, Coix lachrymal, Cornus officinalis, Crataegus pinnatiβda, Cuscuta chinensis Semen, Cynomorium songaricum, Dioscorea bulbifera, Dioscorea opposite Radix, Dioscorea hypoglauca, Drynaria fortune, Eucommia ulmoides, Evodia rutaecarpa, Foeniculum vulgare, Gingko bilobae, Panax ginseng, Gynostemma pentaphyllum Radix, Ligusticum sinesis Radix, Ligusticum wqallichii Radix, Liigustrum lucidum, liliuin brownie, Lyciuin barbarum, Morinda officinalis ^• Radix, Ophiopogonis japonicum, Polygonatum sibiricum, Polygonum multifori Radix, polyporum umbellatum, Psoralea cordifolia, Pueraria lobata Radix, ■-,■

Rehmania glutinosa Radix, Rhodiola rosea, Rubus chingii, Wrighta tinctoria.Cadaba indica, Salvia miltiorrhiza Radix, Schisandra chinensis, Uncaria Rhynchophylla, Zizyphus jejtiba, Zizyphus spinose and the like extracts with medicinal or neutraceutical value.

13. A single layer film of Claim 12 wherein herbal active comprises an extract or extracts of:

a. Zingiber officinale Roxb. and Piper longum Linn. , or

b. Bacopa monnieri Linn and Centella asiatica Linn; „ or

c. Momordica charantia Linn., or

d. Azadirachta indica A Juss., or e. Withania somnifera Diinal., Bacopa monnieri Linn., Nardostachys jatamansi DCor

f. Boerhavia diffusa Linn., Tribulus terrestris Linn., or

g. Picrorhiza kurroa Royle ex Benth., Phyllanthus niruri Linn., or

h. Holarrhena antidysentrica (Roth) A. DC, Euprhorbia hirta Linn., or

i. Asparagus racemosus Willd., Euphorbia hitra Linn., Pueraria tuberose DC, Trigonella foenum- graceiim Linn., Leptadenia raticulata, Withania somnifera Dunal., or

j. Tribulus terrestris Linn., Terminalia arjuna, Pueraria tuberose DC, Trigonella foenum- graceum Linn., Leptadenia raticulata, Withania somnifera Dunal.

14. A film of claim 13 comprising the active ingredient/s incorporated, as % of weight of the film, between a range of 10% to 65%, more preferably between a range of 10% to 45%.

15. A film of claim 14 that is:

a. anti-emetic, comprising extracts of Zingiber officinale Roxb. and Piper longum Linn.,

b. memory supporting, comprising extracts of Bacopa monnieri Linn and Centella asiatica Linn,

c. antidiabetic, comprising extracts of Momordica charantia Linn.,

d. antidiabetic, comprising extract of Azadirachta indica A Juss.,

e, antistress, comprising extracts of Withania somnifera Dunal., Bacopa monnieri Linn., Nardostachys jatamansi DCor f. diuretic, comprising extracts of Boerhavia diffusa Linn., Tribulus terrestris Linn.,

g. hepatoprotective, comprising extracts of Picrorhiza kurroa Royle ex Benth., Phyllanthus niruri Linn.,

h. antidiarrhoeal, comprising extracts of Holarrhena anticlysentrica (Roth) A.

DC, Euprhorbia hirta Linn.,

i. galactogogue, comprising extracts of Asparagus racemosiis Willd., Euphorbia hitra Linn., Pueraria tuberose DC, Trigonella foenum- graceum Linn., Leptadenia raticulata, Withania somnifera Dunal,

j. cardiotonic, comprising extracts of Tribulus terrestris Linn., Terminal Ha arjuna, Pueraria tuberose DC, Trigonella foeniim- graceum Linn., Leptadenia raticulata, Withania somnifera Dunal.

16. A film of claim 15, wherein:

a. anti-emetic film comprises incorporation of extracts of Zingiber officinale Roxb. and Piper longum Linn at about 10 % each by weight of the film composition,

b. memory support film comprises incorporation of extracts of Bacopa monnieri Linn and Centella asiatica Linn at about 10 % each by weight of the film composition,

c. antidiabetic film comprises incorporation of extract of Momordica charantia Linn, at about 15 % each by weight of the film composition,

d. antidiabetic film comprises incorporation of extract of Azadirachta indica A Juss. at about 15 % each by weight of the film composition, e. antistress film comprises incorporation of extract of comprising extracts of Withania somnifera Diinal., Bacopa monnieri Linn., Nanlostachys jatamansi DCor at about 6, 9 and 5 % each respectively by weight of the film composition,

f. diuretic film comprises incorporation of extract of comprising extracts of

Boerhavia diffusa Linn., Tribulus terrestris Linn, at about 10 % each by weight of the film composition,

g. hepatoprotective film comprises incorporation of extract of comprising extracts of Picrorhiza kurroa Roy Ie ex Benth., Phyllanthus niruri Linn, at about 7 % and 13 % each respectively, by weight of the film composition,

h. antidiarrhoeal film comprises incorporation of extract of comprising extracts of comprising extracts of Holarrhena antidysenirica (Roth) A. DC, Euprhorbia hirta Linn, at about 15 % and 5 % each respectively by weight of the film composition,

i. galactogogue film comprises incorporation of extract of comprising extracts of comprising extracts of Asparagus racemosus WiI Id., Euphorbia hitra Linn., Pueraria tuberose DC, Trigonella foenum- graceum Linn., Leptadenia raticulata, Withania somnifera Dunal. at about 7%, 2.5%, 4%, 4%, 3% and 2% each respectively by weight of the film composition,

j. cardiotonic film comprises incorporation of extract of comprising extracts of comprising extracts of Tribulus terrestris Linn., Terminalia arjuna, Pueraria tuberose DC, Trigonella foenum- graceum Linn., Leptadenia raticulata, Withania somnifera Dunal at about 7%, 13%, 4%, 4%, 3% and 2% each respectively by weight of the film composition.

17. A multilayer film of claim 12 comprising extracts of Zingiber officinale Roxb. and Piper longum Linn.; preferably containing the active ingredient in a range of about 20% and 2% respectively by weight of the film composition.

18. A multilayer film of claim 7 comprising non-herbal pharmaceutical active.

19. A multilayer film of claim 18 comprising extract of chlorpheniramine maleate and Phenylephrine preferably containing the active ingredient in a range of about 20% and 2% respectively by weight of the film composition.

20. A process of making an oral dissolving film comprising forming the same film by using a polyvinyl alcohol polyethylene glycol graft polymer having low viscosity and a cellulose derivative as film forming polymers and additives for foπning the film.

21. A process of claim 20 of making single layer or multilayer film comprises selecting at least one step as per requirement of product from the following:

a. formation of slurry of an extract/pharmaceutically active ingredient added to a film forming composition in aqueous or any suitable solvent,

b. debubbling of formed slurry, Casting of slurry done by one of any methods selected from blade over belt method, spray cast method, slot die coating, comma blade process, pouring on substrate method,

c. drying of casted wet film at an elevated temperature, preferably at a temperature of about 40 - 70 ⁰C,

d. cooling of casting line along with dry film at the end of casting line, so as to reduce recoiling of film, e. for making a multilayer film, adding one or more of an inert or / and active containing layer on primary film by gluing or casting, optionally compacting by passing through a roller,

f. drying of multiple layer film,

g. cooling of casting line along with dry film at the end of casting line, so as to reduce recoiling of film,

22. A process of claim 21 wherein the said film forming composition comprises, as per requirement and option, an additional one more water soluble polymer, a surfactant, a stabilizing agent, an emulsifier, a plasticizer, a water soluble sugar, a binder, a sweetener, a flavors, a plasticizer, an antioxidant, a volatile oil and combinations thereof.

23. A process of claim 22 wherein binder used for gluing the films or incorporating in the secondary film for making multi layer films is Polyoxyethylene.

24. A film of claim 1 having unique identification markings on the surface of the films, both artistic and informational markings comprising company name or symbol, product code, product name, potency of the product, calendar wise or day wise prescription schedule printed or embossed on the film surface, printed line printed or embossed on the film or film portions separated by perforations are provided for taking exactly Vi, 1/3 , ¹A portion of film for taking exact dose as prescribed.

25. An oral rapid dissolving film for oral delivery of an active ingredient wherein the said film is having low hygroscopicity and high mucoadhesivity.

26. An oral film of claim 25 wherein the said film absorbs less than 5% moisture, and preferably less than 2%, of its weight and are stable at 75% RH (relative humidity).

27. An oral film of claim 26 wherein the mucodhesivity and higher dissolving rate is imparted by hydroxy alkyl derivative of cellulose, preferably by Hydroxypropyl

Methyl Cellulose, and low- hygroscopicity is imparted by polyvinyl alcohol polyethylene glycol graft polymer, preferably by Kollicoat^® IR.

28. An oral film of claim 1 which takes about 1 to 1.15 minutes for dissolution in an oral cavity after hydration.