FORM-2
209039
31/ Aug /2007
FORM 2
THE PATENT ACT 1970
(39 of 1970)
&
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10 and rule 13)
1. TITLE OF THE INVENTION
A MOUTH MELTING PHARMACEUTICAL DOSAGE FILM COMPRISING MEDICAMENTS AND PROCESS FOR PREPARATION THEREOF.
2. APPLICANT (S)
(a) NAME: LINCOLN PHARMACEUTICALS LIMITED
(b) NATIONALITY: an Indian Company
(c) ADDRESS: Nirav complex, Opp Navrang High School,
Naranpura, Ahmedabad-380014. Gujarat State, India.
3. PREMABLE TO THE DESCRIPTION

PROVISIONAL
The following specification describes the invention.

COMPLETE
The following specification particularly describes the invention and the manner in which it is to be performed.

GRANTED

24 JAN 2007

9-7-2007

Original
1447/MUM/05

The present invention relates to a mouth melting pharmaceutical dosage film comprising medicaments and process for preparation thereof.
More specifically the invention is concerned with a novel oral dosage form; it's pharmaceutical composition containing active Pharmaceutical Ingredients (APIs) in the prophylactic as well as therapeutic concentration.
Most particularly, the invention is concerned with film dosage form containing medicine or medicament and the dosage form is compact, convenient, discrete, effective and fast, metered and value.
Moreover, the present invention is to provide medicine or medicament in mouth melting film dosage form for which water intake is not required. The said dosage form is effective for diabetic as well as calorie conscious people.
Description of the prior Art:
The use of film that is orally soluble such that it disintegrates quickly upon placement in a mouth without leaving substantial residue that is felt on tongue or which needs to be swallowed or rejected from the mouth.
Oral dosage forms have been prepared and marketed in various forms such as tablets, lozenges, pellets, capsules and powders. These dosage forms do not readily disintegrate, dissolve and onset of action is also

comparatively less. Moreover, these dosage forms require intake of water and sometime cause swallowing problems.
U.S. Patent No. 5,807,577 describes improved solid, effervescent and fast melting tablet dosage form and method of making the same. It dissolves in mouth in less than 30 seconds, preferably 20 seconds. The tablet would immediately "melt" in the mouth and disintegrate in a few seconds.
U.S. Patent No. 4,083,949 describes a water-soluble oral form of medicament releases active substance in the gastrointestinal tract at constant rate. The dosage form is in capsule and tablet formulation.
European Patent No. 1145711 describes a flash-melt pharmaceutical dosage form comprising a medicament and a combination of four excipients consisting of superdisintegrant, a dispersing agent, a distributing agent and a binder. The dosage form is prepared in tablet, caplets, wafers form that will disintegrate in the moth in under about 25 seconds.
U.S. Patent 6,045,811 describes a delivery system for an oral care using a flat stripe of material. Flat strip of material is applied to a portion of a tooth, to an entire tooth, or to a row of adjacent teeth.
Thus, there remains a need for a novel dosage form, which melts and absorb in mouth within very short period of time without causing any swallowing difficulties and side effects.

As a solution to this the present invention has been developed which; provides a novel oral dosage form, is in form of film, melts very fast in mouth without intake of water, and it is non-swallowable form. A thin film comprising pharmaceutical compositions melts in 3-5 seconds, preferably 3 seconds once put on tongue. It disintegrates and absorb at the faster rate in mouth. Such Mouth Melting Films avoid swallowing problem and other disadvantages previously experienced with other conventional dosage forms. The film includes at least one flavor, providing a strong flavor sensation once put on tongue. It also includes sweetener providing a sweet sensation in mouth.
Furthermore, the invention provides a process for preparation of mouth melting films comprising medicaments. Detail Description of the invention:
The present invention is a mouth melting pharmaceutical dosage film comprising medicaments and process for preparation thereof
The main objective of the present invention is to form a mouth melting pharmaceutical dosage film containing medicaments, wherein said medicine or medicament is selected from the group consisting of the following category of the drugs, Vitamins, nutraceuticals, as well as Ayurvedic medicaments, like- Cardiovascular, Antidepressants, Antihypertensives, Antidiabetetics, Steroids & Hormones, Analgesics and Antipyretics, Non Steroidal Anti-inflammatory drugs, Anticonvulsant,

1
Cerebral activators, Antimigraine, Anthelmentics, Antibiotics, Antibacterial, Antihistamines, Antiasthamatics, Antitussive, mucolytics, expectorants, tonics and appetite stimulants and anti allergic drugs.
The main objective of the present invention is film dosage form containing medicine or medicament and the dosage form is compact, convenient, discrete, effective and fast, metered, Value and lasts in treatment of anemias caused by poor diet, pregnancy, alcoholism, liver disease, certain stomach/intestinal problems, kidney dialysis.
A process for the preparation of the mouth melting dosage film comprising medicaments comprises the steps of:
(a) Film forming agents and thickeners are dissolved in water ;
(b) Fillers are dispersed in the above solution of step- a and stirred gently to mix;
(c) Plasticisers and surfactants are added to above mass of step-b and stirred to dissolve and mix;
(d) Medicament is dispersed in a proper solvent then added to step-c and stirred to mix;
(e) Stabilizing agents, cooling agents, emulsifying agents, flavoring agents, coloring agents, sweeteners and preservatives are added to mixture prepared in step-d and stired to dissolve and mix;

(f) The viscous mass obtained after step-e is passed through colloidal mill;
(g) The viscous mass is spreaded on plain surface, dryed at controlled temperature and cut into uniform pieces.
The following illustrative examples represent a most preferred embodiment of the present invention. Example 1:
Mouth melting dosage film containing folic acid composition and process for the preparation thereof is described as following.
The composition of Folic acid is prepared by using the active pharmaceutical ingredient Folic acid in amount about 0.1 mg to 10 mg., other pharmaceutical excipients such as Sodium Alginate, Sodium Carboxy Methyl Cellulose, Polacryl, Carrageenan and maltodextrin as film former, Mannitol and Aspartame as sweeteners, Citric Acid as a pH adjustant, Cresmer EL and Hydroxylated Soya Lecithin as Emulsifiers, Glycerine as a plasticiser, Sodium Benzoate, as a Preservative, BHT as a antioxidant to maintain freshness of the flavour, Flavour Pineapple as a flavouring agent and Purified water as a vehicle.

Each 50 mg Film Contains:
Ingredients Quantity (w/w)
Folic Acid 10.95 %
Sodium Alginate 20 %
Sodium Caboxy Methyl Cellulose 0.87 %
Polacryl 3.60 %
Carrageenan 0.92 %
Mannitol 12.00 %
Aspartame 1.80 %
Citric Acid Monohydrate 6.00 %
Maltodextrin 28.8 %
Cresmer EL 2.00 %
Glycerine 3.60 %
Hydroxylated Soya Lecithin 1.00 %
Sodium Benzoate 0.25 %

BHT

0.01

%

Flavour: Pineapple Purified Water

2.16 %
Quantity sufficient

Process for the preparation mouth melting film comprising Folic acid as a medicament:
(a) Sodium Alginate, Sodium Caboxy Methyl Cellulose, Polacryl and Carrageenan are dissolved in water.
(b) Mannitol, Aspartame, Maltodextrin, Sodium benzoate, Hydroxylated Soya Lecithin and Pineapple flavour are dissolved in water and add in to solution prepared in step-a.
(c) Folic acid is dissolved in Citric acid solution and also add into Solution prepared in step-a.
(d) Glycerine and Cresmer are added to solution prepared in step-a.
(e) BHT is dissolve in PG and add into solution prepared in step-a.
(f) Passing the above-prepared solution from colloidal mill.
(g) Film is made of this viscous suspension by spreading on plain surface by using sophisticated machines. The film is dried in a controlled temperature and cut in to uniform weight and dimension pieces, so that each piece. Finally the films are packed in the desired quantity and labelled accordingly.
Example II:
Mouth melting dosage film containing Ayurvedic composition and process for the preparation thereof is described as following. Each 50 mg Film Contains:

Ingredients Quantity (w/w)

Menthol 12.5 %
Camphor 0.3 %
Peppermint oil 4.44 %
Eucalyptus oil 4.44 %
Eucalyptus oil 3.28 %
Thymol 0.38 %
Sodium Alginate 0.02 %
Sodium CMC 0.874 %
Polacryl Potassium 3.6 %
Carrageenan 0.92 %
Mannitol 12 %
Aspartame 1.8 %
Maltodextrin 28.78 %
Citric acid monohydrate 6 %
Sodium Saccharine 2.18 %
Cresmer-EL 0.005 %
Glycerine 0.005 %
BHT 0.036 %
Simethicone 0.1 %
Lecithin 1.0 %

Propylene Glycol 5.0 %
Colour: Brilliant Blue 2.0 %
Purified Water Qs %
Process for the preparation of mouth melting film containing
Ayurvedic composition as medicament:
(a) Sodium Alginate, Sodium Caboxy Methyl Cellulose, Polacryl Potassium, Carrageenan are dissolved in to water.
(b) Mannitol, Aspartame, Maltodextrin and sodium Benzoate, Citric acid monohydrate, Sodium Saccharine and Hydroxylated Soya Lecithin are dissolve in water and add in to solution prepared in step-a
(c) Dissolve Menthol in Propylene Glycol and add Camphor, eucalyptus oil, Peppermint oil, Thymol, BHT and eucalyptus. Add all this into solution prepared in step-1.
(d) Add Glycerine and Cresmer to solution prepared in step-1.
(e) Dissolve Brilliant Blue in water and add to it.
(f) Pass the above-prepared solution from colloidal mill. Film of this viscous suspension is made by spreading on plain surface or by using sophisticated machines. The film is dried in a controlled temperature and cut in to uniform weight and dimension pieces. Finally the films are packed in the desired quantity and labelled accordingly.

In the preparation of mouth melting film various active and inactive pharmaceutical ingredients are used. Mouth melting films include many ingredients. The basic ingredients for forming a film include water (which can be later dried out of the film) and a film forming agent. Many other additives are used as well for purposes of saliva stimulation, plasticizing, stabilizing, emulsifying, fillers, thickening, binding, coloring, or acting as a surfactant.
The film include film-forming agent, water, additional film-forming agents, plasticizing agents, flavoring agents, acids, sulfur precipitating agents, saliva stimulating agents, cooling agents, surfactants, stabilizing agents, emulsifying agents, thickening agents, binding agents, coloring agents, sweeteners, preservatives, fragrances, and the like. Fruit or food flavors are also used to add the flavour. # Film Forming Agent:
The effective amount of the bulk filler agents is in the range from approximately 10% to about 90%. An example pullulan free edible film composition can include an effective amount of carageenan as a film forming agent; an effective amount of microcrystallme cellulose as a bulk filler agent; and an effective amount of polyethylene glycol as a plasticizing agent.
Film-forming agents include, hydroxypropylmethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, polyvinyl pyrrolidone,

carboxymethyl cellulose, polyvinyl alcohol, sodium alginate, polyethylene glycol, xanthan gum, tragacanth gum, guar gum, acacia gum, arabic gum, polyacrylic acid, methyl methacrylate copolymer, carboxyvinyl polymer, amylose, high amylose starch, hydroxypropylated high amylose starch, dextrin, pectin, chitin, chitosan, collagen, gelatin, zein, gluten, soy protein isolate, whey protein isolate,, polysaccharides, natural gums, polypeptides, polyacrylates,, karaya gum, gelatin, mixtures thereof and others.
A film former pullulan is used in amounts ranging from about 0.01 to about 99 wt %, about 30 to about 80 wt %, from about 45 to about 70 wt % of the film or from about 60 to about 65 wt % of the film.
Film forming agents, which can be used within a pullulan-free Edible film include, but are not limited to, cellulose ethers; modified starches; natural gums; gelatins; edible polymers; hydrocolloid flours; seaweed extracts; land plant extracts; derivatives thereof; and combinations thereof.
Examples of cellulose ethers include, but are not limited to,
methylcellulose; methylcellulose; hydroxymethylcellulose;
hydroxyethylcellulose; hydroxypropylmethylcellulose;
carboxymethylcellulose; derivatives thereof and combinations thereof.
Modified starch examples include, but are not limited to, acid and enzyme hydrolyzed corn and potato starches. Further, examples of natural

gums include, but are not limited to, gum arabic; guar gum; locust bean gum; carageenan gum; acacia; karaya; ghatti; tragacanth agar; tamarind gum; xanthan gum; derivatives thereof; and combinations thereof.
Examples of edible polymers include, but are not limited to, microcrystalline cellulose; cellulose ethers; xanthan; derivatives thereof; and combinations thereof. Moreover, examples of hydrocoUoid flour include, but are not limited to, guar gum; locust bean; microcrystalline cellulose; derivatives thereof and combinations thereof.
Seaweed extract examples include, but are not limited to, alginates; carageenans; derivatives thereof; and combinations thereof. Land plant extract examples include, but are not limited to, pectin; arabinoglactan; derivatives thereof; and combinations thereof.
If the film has a relatively high oil content, it may be useful to avoid substantial amounts of humectant in the film (and more preferable to have no humectant in the film), so as to avoid producing an overly moist, self-adhering film. In particular, it may be useful to formulate the film with a plasticizing agent other than glycerin, which is also a humectant, and with a sweetener other than Sorbitol, which is a mild humectant.
Film forming agent ranges in amount from about 10% to about 90%, more preferably 25% to about 75% dry weight of the film composition.

It will be evident to those skilled in the art, that other edible water-soluble film forming agents who exhibit desirable properties may be utilized. A bulk filler agent may be present, especially in pullulan free edible film compositions, to reduce the "slimy" texture of the compositions. #Binders:
Binding agents used in the present invention includes starch, in amounts ranging from about 0.1 to about 10 wt % or otherwise, other binders casein and pullulan. Thickeners:
To further enhance the structure of the film compositions, an effective amount of at least one thickening agent is used. Suitable thickening agents include, but are not limited to, cellulose ethers, such as hydroxyethyl cellulose, hydroxypropylmethyl cellulose, or hydroxypropyl cellulose, either alone, or mixtures thereof. Other thickening agents include methylcellulose, carboxyl methylcellulose, and the like, in amounts ranging from about 0.1 to about 20 wt % or otherwise. Polymers such as carbomer, polyvinyl pyrrolidone, carboxymethyl cellulose, polyvinyl alcohol, sodium alginate, polyethylene glycol, natural gums like xanthan gum, tragacanth, guar gum, acacia gum, arabic gum, water-dispersible polyacrylates like polyacrylic acid, methyl methacrylate copolymer, carboxyvinyl copolymers. The concentration of a water-soluble polymer in the final film can be as desired or can vary between 20 and 75% (w/w).

#FiIlers:
The bulk filler agent of the present invention is microcrystalline cellulose. A bulk filler agent is added to the film-forming agent for many purposes, including to reduce the "slimy" texture of the compositions. The bulk filler range in amount from about 10% to about 90% by dry weight of the film composition. Suitable bulk filler agents include, but are not limited to, magnesium carbonate; calcium carbonate; calcium phosphate; calcium sulfate; magnesium silicate; aluminum silicate; ground limestone; clay; talc; titanium dioxide; microcrystalline cellulose; cellulose polymers such as wood; derivatives thereof; and combinations thereof. #Plasticizers:
To improve flexibility and reduce brittleness of the edible film compositions, a softener, also known as a plasticizing agent, is used. The effective amount of the plasticizing agent of the present invention is used in an amount ranges from about 0.1% to 20% dry weight of the film composition.
Suitable plasticizing agents of the present invention include, but are not limited to, polyols such as Sorbitol; glycerin; polyethylene glycol; propylene glycol; monoacetin; diacetin; triacetin; hydrogenated starch hydrolysates; corn syrups; derivatives thereof; and combinations thereof. A polyalcohol can be used to achieve the desired level of softness of the film. Examples of polyalcohol include glycerol, polyethylene glycol, propylene

glycol, glycerol monoesters with fatty acids or other pharmaceutically used polyalcohoL The concentration of the polyalcohol used in the dry film ranges in amount from about 0.1 to 5% (w/w). Some of the Plasticizers are water soluble and are miscible with a polymer.
Likewise, other plasticizing agents typically cited for film forming
agents impart a bitter or otherwise very bad taste to the film, or, in the case
of humectant plasticizers such as glycerin, attract moisture into the film in
humid environments and cause the film pieces to undesirably adhere to
adjacent film pieces. Many of the highly-concentrated, oil-soluble flavors
act as a plasticizer in their own right in the snacks, eliminating or
substantially reducing the need for taste-detracting or bitter or bad tasting
prior art plasticizers or humectant plasticizers.
Some suitable plasticizers include, for example and particularly for oral-mucosal contact and other use in the oral cavity, glycerin, Sorbitol, any of the glycols, polysorbate 80, triethyl titrate, acetyl triethyl titrate, and tributyl titrate. #Surfactants:
Surfactants are optionally included in the films. Surfactants reduce the surface tension of water when used in very low concentration. They also encapsulate or coat a material in a liquid. Useful surfactants include mono and diglycerides of fatty acids and polyoxyethylene sorbitol esters and Polysorbate 80. When a combination of surfactants is used, the first

component is polyoxyethylene sorbitan fatty acid ester or a alpha-hydro-omega-hydroxypoly (oxyethylene) poly (oxypropylene) poly (oxy-ethylene) block copolymer, while the second component is polyoxyethylene alkyl ether or a polyoxyethylene castor oil derivative. Other surfactants include, Polysorbate 80, Sorbitan fatty acid ester, pluronic acid, sodium lauryl sulfate, and the like. A surfactant is added in an amount ranging from about 0.5 to 15 wt. In order to achieve desired instant wettability. The ratio between a first and second component of the binary surfactant mixture is kept within 1:10 and 1:1, or within 1:5 and 1:3. The total concentration of surfactants in the final film depends on the properties of the other ingredients, but it ranges between 0.1 and 5% (w/w). #Stabilizing Agents:
In the present invention stabilizing agents include are xanthan gum, locust bean gum and Carrageenan, in amounts ranging from about 0.1 to 10 wt % or otherwise. Other stabilizing agents include guar gum. #CooIing Agent:
In the said invention cooling agent include is monomenthyl succinate, in amount ranging from about 0.001 to about 2.0 wt % or otherwise. #Emulsiflers:
Emulsifiers improve manufacturability and consistency of the film. Emulsifying agents included in the present invention are casein,

triethanolamine stearate, quaternary ammonium compounds, acacia, gelatin, lecithin, bentonite, veegum, and the like. It is used in an amount ranging from about 0.1 to 5wt % or otherwise. #Flavorings:
The film provides craving-satisfying by including small amount of fats, oils, salt, meat flavorings or other flavorings without the customer ingesting significant amounts of those substances. Other unusual flavors can be provided as well, such as 'apple pie ala mode' or 'roast beef with green peppers and onions. By providing such flavors, the films assist dieters in satisfying a craving without breaking a diet. Likewise, highly sour flavors can be provided without interfering with their appetite while not substantially lowering the pH of the film. Lowering the pH of the film may interfere with the film properties. One aspect of the present invention in preparation of films is the use of more than one flavor in a film. The use of multiplicity of flavor within the mouth enhances the ingestion experience. Not by way of limitation, this can be accomplished two ways: First, by using multiple feed streams of differently flavored films when casting or extruding the films; and second, by providing multiple-layer film with each layer of a different flavor. In the latter case, the film can be co-cast or co-extruded, or can be bonded together with a water-soluble edible binder. For example, one layer is used of caramel flavor and the other layer is of blackberry flavor. As another

example, a single layer film can be striped with alternating layers that are raspberry flavored with a red color and cream flavored with a white color.
An aspect of the films is the inclusion in an Mouth Melting film of any one or more of fats, salt, or substitutes or artificial flavoring providing a similar effect for flavor. For example, butter or cream can be included in the film. Or, an artificial butter flavor or artificial cream flavor. Examples of the use of cream flavors have been given above. Often these fats will be used in conjunction with other flavors as an enhancement. As another example, peanut oil or corn oil and salt can be included in a popcorn-flavored film for a more robust taste and better satisfaction of cravings. For the health conscious consumer, artificial butter flavoring and salt substitute such as potassium chloride can be used in the popcorn-flavored film. While water-based, spray-dried, alcohol/glycol-based, or semi-concentrated flavors can fulfill these aspects of the snacks, we have discovered that highly-concentrated oil-soluble flavors, whether natural or artificial or combinations thereof, can be satisfactory. Such highly-concentrated oil-soluble flavors provide sufficient flavoring to be considered intense, particularly in combination with the sweetening regimen provided below. The highly-concentrated, oil-soluble snack, candy, fruit or food flavors provide the required intensity of flavor without the bitterness associated with attempts to obtain that level of flavor with water-based, spray-dried, alcohol/glycol-based, or semi-concentrated flavors. Further, since the oil-

soluble flavor is not water soluble, it lingers in the mouth much longer, providing an extended period of flavor satisfaction or craving satisfaction. Typically these Mouth Melting films are brittle unless plasticized. The flavorings used in the present invention incluses those known to the skilled artisan, such as natural and artificial flavors. These flavorings are chosen from synthetic flavor oils and flavoring aromatics, and/or oils, oleo resins and extracts derived from plants, leaves, flowers, fruits and so forth, and combinations thereof. Representative flavor oils include: spearmint oil, cinnamon oil, peppermint oil, clove oil, bay oil, thyme oil, cedar leaf oil, oil of nutmeg, oil of sage, and oil of bitter almonds. Natural or synthetic fruit flavors such as vanilla, chocolate, coffee, cocoa and citrus oil, including lemon, orange, grape, lime and grapefruit and fruit essences including apple, pear, peach, strawberry, raspberry, cherry, plum, pineapple, apricot and so forth. These flavorings can be used individually or in admixture. Commonly used flavors include mints such as peppermint, wintergreen, spearmint, birch, anise and such fruit flavors, as cherry, lemon-lime, orange, grape, artificial vanilla, cinnamon derivatives, and others, whether employed individually or in admixture. Flavorings such as aldehydes and esters including cinnamyl acetate, cinnamaldehyde, citral, diethylacetal, dihydrocarvyl acetate, eugenyl formate, p-methylanisole, and so forth can also used. Further examples of aldehyde flavorings include, but are not limited to acetaldehyde (apple); benzaldehyde (cherry, almond); cinnamic

aldehyde (cinnamon); citral, i.e., alpha citral (lemon, lime); neral, i.e. beta
citral (lemon, lime); decanal (orange, lemon); ethyl vanillin (vanilla,
cream); heliotropine, i.e., piperonal (vanilla, cream); vanillin (vanilla,
cream); alpha-amyl cinnamaldehyde (spicy fruity flavors); butyraldehyde
(butter, cheese); valeraldehyde (butter, cheese); citronellal (modifies, many
types); decanal (citrus fruits); aldehyde C-8 (citrus fruits); aldehyde C-9
(citrus fruits); aldehyde C-12 (citrus fruits); 2-ethyl butyraldehyde (berry
fruits); hexenal, i.e. trans-2 (berry fruits); tolyl aldehyde (cherry, almond);
veratraldehyde (vanilla); 2,6-dimethyl-5-heptenal, i.e. melonal (melon); 2-
6-dimethyloctanal (green fruit); and 2-dodecenal (citrus, mandarin); cherry;
grape; mixtures thereof; and the like.
The amount of flavoring employed is normally a matter of preference subject to such factors as flavor type, individual flavor, and strength desired. Thus, the amount of flavour used is varied in order to obtain the result desired in the final product. Such variations are within the capabilities of those skilled in the art without the need for undue experimentation.
In the present invention the flavours are used in an amounts ranges
from about 0.1 to 30-wt %; preferably from about 2 to 25 wt %, Most
preferably from about 8 to 10 wt%.
#Sweeteners:
Artificial sweeteners such as aspartame, acesulfame potassium, saccharine and sucralose can impart an aftertaste when used alone to impart

sufficient sweetness to a sweetened film. In addition to this problem, different sweeteners impart their peak sweetness at different times after hydration with saliva. Use of one sweetener alone thus will not impart the sweetness desired over the entire time that optimized flavors stay in the mouth, being too early or too late. Prior films try to address this with a combination of two of these sweeteners.
Thus a preferred aspect of the present invention is to use admixture
of all three of these sweeteners in small amounts to achieve the full level of
sweetness desired without substantial aftertaste. Both natural and artificial
sweeteners are used in the invention.
A. Water-soluble sweetening agents such as monosaccharides,
disaccharides and polysaccharides such as xylose, ribose, glucose
(dextrose), mannose, galactose, fructose (levulose), sucrose (sugar),
maltose, invert sugar (a mixture of fructose and glucose derived from
sucrose), partially hydrolyzed starch, corn syrup solids, dihydrochalcones,
monellin, steviosides, and glycyrrhizin;
B. Water-soluble artificial sweeteners such as the soluble saccharin salts,
i.e., sodium or calcium saccharin salts, cyclamate salts, the sodium,
ammonium or calcium salt of 3,4-dihydro-6-methyl-l,2,3- -oxathiazine-4-
one-2,2-dioxide, the potassium salt of 3,4-dihydro-6-methyl-l,2,3-
oxathiazine-4-one-2,2-dioxide (acesulfame-K), the free acid form of
saccharin, and the like;

C. Dipeptide based sweeteners, such as L-aspartic acid derived sweeteners,
such as L-aspartyl-L-phenylalanine methyl ester (aspartame) and materials
described in U.S. Pat. No. 3,492,131, L-alpha-aspartyl-N-(2,2,4,4-
tetramethyl-3-thietanyl)-D-alaninamide hydrate, methyl esters of L-
aspartyl-L-phenylglycerin and L-aspartyl-L-2,5,dihydrophenyl-glycine, L-
aspartyl-2,5-dihydro-L-phenylal- -anine, L-aspartyl-L-(l -cyclohexyen)-
alanine, and the like;
D. Water-soluble sweeteners derived from naturally occurring water-
soluble sweeteners, such as a chlorinated derivative of ordinary sugar
(sucrose), known, for example, under the product description of sucralose;
and
E. protein based sweeteners such as thaumatoccous danielli (Thaumatin I
and II). Other sweeteners are used as Preservatives:
#Preservatives:
To prevent microbial growth during manufacturing and storage preservatives in single or in combination are used in the preparation of mouth melting film. The preservatives used in the concentration ranging in amount from about 0.05 % w/w to 0.25 % w/w.
The class II grade preservatives like benzoic acid and its salts, para hydroxy benzoic acids and its salts, sorbic acid and its salts and broad-spectrum preservatives like Bronopal are also used in the preparation of mouth melting film dosage form.

#Sour Films:
One difficulty in making good tasting flavor films is in providing highly sour flavors, for example sour apple or sour lemon or sour peach. Sourness, or tartness, is generally caused by low pH. Low pH is known to adversely affect nearly all of the film forming ingredients, causing for example brittleness, low tensile strength, and short shelf life. One solution that we have discovered is to combine the snack, candy, fruit or food flavors, the acid required to cause the desired tartness, and pullulan (as a film forming ingredient), since this combination is less effected (though still somewhat effected) than other combinations which use as the film former starches or gums. Another solution we have discovered is to have the acid in a separate layer from the film.
For example, as the film is drying, the acid can be applied in powder form (optionally diluted by a filler material such as maltodextrin) to the exterior of the film (optionally with a binder material to enhance the adhesion to the film). In this way, the acid does not penetrate the film itself to a degree great enough to deteriorate the film. This discovery is particularly exciting because the acid in this case may be the first thing to contact the tongue, so the burst of sour is first even before the flavor, which is desirable in many types of candy snacks. We have also invented a way to make the sour flavor last longer. This is done through the same method of having the acid in a separate layer, except that some or all of the acid is microencapsulated to

create a delay in salvation. Using a mixture of acids with different degrees of delay in salvation can make the sour flavor last. The sour flavor can last at least as long as the highly-concentrated oils which linger in the mouth. The acid can also be put between two layers of film, which are bound together by the binding agent that is with the acid. In this case, the film flavor would be tasted first, then the sour, which is desirable in some instances. Common edible acids are citric, tartaric and malic, and we have found that tartaric acid is especially advantageous, especially when it is an ingredient of the film rather than coated on the exterior. Tartaric acid provides considerable acidity for the amount of volume occupied, which in such thin films is advantageous. Film is then cut variety of shapes and sizes and packed.
Although the invention has been described above with respect with two examples, it will be evident to a person skilled in the art that it may be modified using above stated other ingredients; which should not be limited in scope.