FORM 2
THE PATENTS ACT, 1970 (39 of 1970)
&
THE PATENTS RULES, 2003
PROVISIONAL SPECIFICATION
[See section 10, Rule 13]


RAPID DISSOLVABLE ORAL FILM FOR DELIVERING HERBAL EXTRACT/S WITH OR WITHOUT OTHER PHARMACEUTICALLY ACTIVE AGENTS;
UNIJULES LIFE SCIENCES LTD, A
CORPORATION ORGANIZED AND EXISTING
UNDER THE LAWS OF INDIA, WHOSE
ADDRESS IS NO. 1505/1, UNIVERSAL
SQUARE SHANTINAGAR, NAGPUR.
MAHARASHTRA, INDIA.

THE FOLLOWING SPECIFICATION
DESCRIBES THE INVENTION.


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 herbs for treatment of many diseases and disorders of mammals. The herbal formulations includes Asava, Arishtha, Churna, Gutika, Kadha, Prasha, Vati, Paka, Avaleha, Ghrita, Murabba, Sharbat, SulTof, Araq, Habba, Rouqhun, Qurs. which suffer a common disadvantage of lack of patient compliance as the formulations like Churnas are needed to be taken in bulk amount with glassful of water. Modern formulation 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 formulation 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.
In U.S. Pat No.6, 177, 096 Bl, Zherbe 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, 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 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 is packed along with carrier and does pertain with single polymeric film. In patent US7025983 B2, Leung et at. have disclosed a film and method for preparing a physiologically compatible film, said method comprising: mixing water soluble polymer and
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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 discloses films with an effective amount of an
antimicrobial agent wherein the antimicrobial agent comprises cinnamaldehyde in
200400865 46;,cardamom oil in 20040253192 discloses a Pullulan free edible film
composition comprising a film forming agent; and an effective amount the antimicrobial
agent comprising cardamom oil and carvacrol 20040253278 .
In United States patent application No. 20030235606; 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 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 uses multiherbal
preparations for treatment, these multiherbal preparations pertains 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
being maneuvered in the mouth cavity for placement at most appropriate place, it in most
probabilities, comes in at least a momentary contact with wet 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.. Also, the prior art films can be rejected by
non-compliant patients after delivery of the film in their oral cavity. Film of this invention
takes a few seconds longer to hydrate so that adequate time is available for its maneuvering
inside oral cavity for locating it at preferred location, is rapidly dissolving after hydration.
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..
Further the polymeric film type of product in prior art methods of manufacturing faces the
problem of curling at the end of scrapping (end of casting line). The present discloses
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invention utilizes a novel flash freeze method, which minimizes the curling of the film at the end of casting line.
The present invention also relates to improvement in the stability of volatile components in the film while the same is being manufactured. The stability of the volatile component is achieved through the use of lower drying temperatures, as mentioned earlier the flash freeze method in which the secondary layer is applied on the cooled primary film. Such flash freeze method decreases the bed temperature. Moreover the solvent used in the secondary layer film composition is nonaqueous and requires low temperatures for evaporation. Thus, the primary film is exposed to lower drying temperature while drying of secondary film is going on, and thereby the volatile component in primary as well as secondary film is stabilized as compared to existing process of film making. The present surface dissolving film exhibits very low hygroscopicity and high mucoadhesivity. 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 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 surface dissolving film exhibits a unique property of getting hydrated only after few seconds upon exposure to moisture. Such 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 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), other hydrocolloids. The film forming agents of the present invention are preferably polyvinyl alcohol polyethylene glycol graft polymer having viscosity in the range of (130 -190) more preferably of 162 millipascal seconds (mPa-s) as determined as a 20% 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
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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 as a 2% by weight aqueous solution of the HPMC at 20°C can be used. Preferably the HPMC having viscosity of about 3 to about 20(mPa-s) at 20°C 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, extract/s, with or without a flavoring agents particularly an essential oil which act as breath freshening agent. The film further comprises of solvent, additional film forming agents, 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, pullalan, polyvinyl alcohol polyethylene glycol graft polymer and soluble cellulosic polymer, wherein their ratio (by weight) may vary from about 1:3 to about 6:2 and preferably about 3.5:1 to about 6:1.5. The Polyoxyethylene polymers are selected according to the viscosity and the molecular weight The hydrocolloids 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.
In one of the embodiment of this invention herbal extract/s is prepared by any method of extraction. The term extract is used herein in this particular invention includes all of the many types of preparations containing an effective amount of active ingredients produced by biogenesis. 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. The extract incorporated are also not limited to any specific part of plant, the extract can be derived from all parts includes flowers, leaves, stem, bark, roots, inflorescence; 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 pharmaceutical^ active
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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., Mucuna prureins Baker., Terminalia arjuna, Achyranthes bidentatae
Wall, Achyranthes aspera Linn, Achyranthes prophyristachya Wall, Aconitum napellus Linn,
Acorus americanus, Actinidia 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,
Asparagusracemosiis 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 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 sibiricum, Polygonum
multifori Radix, polyporum umbellatum, Psoralea cordifolia, Pueraria lobata Radix,
Rehmania glutinosa Radix, Rhodiola rosea, Rubus chingii, Salvia miltiorrhiza Radix,
Schisandra chinensis, Uncaria Rhynchophylla, Zizyphus jejuba, Zizyphus spinosa and like.
Appropriate pharmaceutical^ active ingredients for use in the edible film of the present
invention include, but not limited to, one or more than one pharmaceutically active agents
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,
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Bromocriptine, Cobergoline, Selegiline, Triphenidyl HCL, Codergocrine, Fentanyl, Flunarizine, Rizatriptan, Lornoxicam, Tizanidine, Donepezil, Rivastigmiine, Betamethasone, Terazocin, Glimeperide, Finasteride, Salbutamol, Ketotifen, Montelukast, Cetrizine, Clemastine, Cyproheptadine, Pes lorati dine, 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, thickeners, 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 comprises of synthetic flavor oils and flavoring aromatics, and/or essentia! 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. A combination of amount ranging from about 1% to about 10% by weight and preferably about 2% to about 8% by weight. The sweeteners may be incorporated in single layer and multilayer in an amount ranging 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) is also advantageous in the presently described technology. The high water soluble sugars present in the film of the present invention is in the 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 comprises 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. The surfactants 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 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.
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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 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 about 0.2% to about 4% by weight.
In certain embodiments of the present invention provided a single or multiple layer film including 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. In another embodiment of the present invention 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 form of printed line printed or embossed on the film or film portions separated by perforations are provided for taking exactly lA, 1/3 , % portion of film for taking exact dose as prescribed by the physician.
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FIGURES AND LEGENDS
Figure. 1 is a perspective of single layer rapid dissolving film, Figure la 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 on 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 form
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
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9 - Casted wet film
10 - Drying zone (chambers)
11 - Dry thin edible film 12- Flash cooling zone
13 -Dried, cooled thin edible film at the end of casting line.
14-Scrapper
15-Scrappedfilm
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 slurry. Casting apparatus (process) is selected from spray coat method, comma blade method, doctor blade method, slot die coating and the like processes.
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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 slited and further cut to form a single unit of thin edible film.
In 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) according to present invention comprise 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 formation. 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 coaler, 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 containing herbal extracts on one or either side of the core (primary) film.
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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 °C according to need of
formulation.
d. Cooling of casting line along with dry film at the end of casting line, so as to
reduce recoiling 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 °C 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 includes, for example, without limitations, novel compositions of herbal extract/s with or without pharmaceutical ly 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
KollicoatIR 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
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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 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 lb: 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 .£/««. extract 100
Hydroxypropyl methyl cellulose 550
KollicoatIR 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 casted by using tape casting line to form a film of desired thickness. The
14

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 lc: 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
KollicoatIR 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)
15
Active substance and additives weight in grams
Azadirachta indica A Juss. extract 150
Hydroxypropyl methyl cellulose 550
KollicoatIR 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 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 le: 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
Bacopa monnieri Linn, extract 90
Nardostachys jatamansi DC extract 50
Hydroxypropyl methyl cellulose 550
KollicoatIR 100
Trehalose 55
16

Tween80 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 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
KollicoatIR 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 terrestris 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 lg: 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
KollicoatIR 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
18

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., Phyllanihus niruri 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 lh; 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
KollicoatIR 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,
19

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 li: 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
Trigonellafoenum- graceum Linn. Extract 40
Leptadenia raticulata wight and Am. Extract 30
Withania somnifera Dunal. Extract 20
Hydroxypropyl methyl cellulose 525
KollicoatIR 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 Asparagus racemosus Willd, Euphorbia hitra Linn., Pueraria tuberose DC, Trigonella foenum- graceum Linn., Leptadenia raticulata wight and Am. and Withania somnifera Dunal. Successively measured
20

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

Active substance and additives weight in grams
Tribulus terrestris Linn, extract 70
Terminalia arjuna Wand A. extract 130
Pueraria tuberose DC. extract 40
Trigonellafoenum- graceum Linn. Extract 40
Leptadenia reticulata wight and Am. Extract 30
Withania somnifera Dunal. Extract 20
Hydroxypropyl methyl cellulose 525
KollicoatIR 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 Tribulus terrestris Linn, and Terminalia arjuna W and A.. Successively measured amounts of HPMC, Koliicoat IR,
21

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
KoIlicoatlR 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 longum 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
KollicoatIR 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 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 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
A dditives 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
pharmaceutical/y active ingredient / pharmaceutica//y 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
24

The core film of any individual herb or combination of non interacting 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
KoilicoatlR 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.
25

Application of additional (secondary^ film of Piper lonzitm 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 warmed and stirred for 15 minutes. To this warm slurry added the required volume of ethanol (absolute) to produce slurry of J 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.
26

Example 4: PREPARATION OF MULTILAYER ANTICOLD FILM OF NON-HERBAL PHARMACEUTICAL ACTIVES.
Example 4a: PREPARATION OF MULTILAYER AN1TCOLD 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
KollicoatIR 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
27

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
KollicoatIR 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
28

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 non interacting pharmaceutical ly 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 pharmaceutical^ active ingredients as needed according to formulation. 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
29

Hydroxypropyl methyl cellulose 550
KollicoatlR 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 fsecondarvl film of Phenylephrine
Materials taken per 1 liter batch of additional (secondary) film forming slurry of Piper
longum 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
30

Aspartame 5
Bronopol 0.5
Sunset yellow (colour) 0.1
Ethanoi 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 ethanoi 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 ]5 minutes. To this warm slurry added the required volume of ethanoi (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 puJIulan free (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 assessment protocol comprised of four batches of single layer rapid dissolving film as described in examples la, lb, lc and Id and multilayer film prepared by gluing method as described in examples 2a, 3a, 4a, 4b and example which uses cast over film method. 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 7 is the comparison of tensile strength of same film formulation batch (Example la, lb, lc, Id) on the day of production and after six months accelerated stability study. Shown in the figure 8 is the comparison of folding endurance of same film formulation batch (Example la, lb, lc, Id) on the day of production and after six months accelerated stability study. No significance difference was observed in the physical and film properties of all formulations.
Table 1

Formulation code

Folding
enduranc
e

Tensile strength

Self adherance

Dissolving
time (in
seconds)

Example 1 7 6.2136 No 30
Example 2 7 6.6823 No 30
Example 3 8 7.8945 No 40
Example 4 9 8.4589 No 45
Table 2

Formulation code

Folding
enduranc
e

Tensile strength

Self adherence

Dissolving
time (in
seconds)

Example 1 6 6.1562 No 30
Example 2 5 6.1838 No 25
Example 3 7 7.2967 No 35
Example 4 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.
32

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

23% 43% 75% 93%
Example 1 2.84 3.14 3.89 5.34
Example 2 2.97 3.38 4.22 5.64
Example 3 3.16 3.91 4.80 5.88
Example 4 3.61 4.76 4.92 5.78