DESC:FORM 2

THE PATENTS ACT 1970
(SECTION 39 OF 1970)

&

THE PATENT RULES, 2003

COMPLETE SPECIFICATION
(Section 10 and Rule 13)

COMPOSITION OF TIOCONAZOLE VAGINAL FILM AND PROCESS FOR PREPARATION THEREOF

We, HETERO HEALTHCARE LIMITED.,
a company incorporated under the company’s Act, 1956
having address at Sy.No:83/1, Plot Nos. 16/A/1 & 16/A/2, 19th & 20th Floor,
Hetero Tower, Commerzone, Silpa Gram Craft Village,
Madhapur, Shaikpet, Hyderabad, Telangana State, India- 500081

The following specification particularly describes the invention and the manner in which it is to be performed.
FIELD OF THE INVENTION
The present invention relates to a pharmaceutical composition of Tioconazole.

The present invention specifically relates to a pharmaceutical composition of Tioconazole vaginal film.

The present invention specifically relates to the pharmaceutical composition of Tioconazole vaginal film comprising Tioconazole and pharmaceutically acceptable excipients.

The present invention more specifically relates to the pharmaceutical composition of Tioconazole vaginal film comprising Tioconazole and pharmaceutically acceptable excipients selected from film-forming agents, solubilizing agents, plasticizers and solvents.

The present invention also relates to the process for the preparation of Tioconazole vaginal film.

BACKGROUND OF THE INVENTION
Candidiasis is an infection caused by a yeast (a type of fungus) called Candida. Candida normally lives on skin and inside the body such as in the mouth, throat, gut, and vagina, without causing any problems. Candida can cause an infection if conditions change inside the vagina to encourage its growth. Things like hormones, medicines, or changes in the immune system can make infection more likely. The common term for candidiasis in the vagina is a vaginal yeast infection. Other names for this infection are vaginal candidiasis, vulvovaginal candidiasis, or candidal vaginitis.

The most common symptom is vaginal itching, which may be severe. Other symptoms include burning with urination, a thick, white vaginal discharge that typically does not smell bad, pain during sex, and redness around the vagina. Symptoms often worsen just before a woman's period.

Vaginal yeast infections are due to excessive growth of Candida. These yeasts are normally present in the vagina in small numbers. Vaginal yeast infections are typically caused by the yeast species Candida albicans. Candida albicans is a common fungus often harbored in the mouth, digestive tract, or vagina without causing adverse symptoms.

Tioconazole is a broad-spectrum imidazole antifungal agent that inhibits the growth of human pathogenic yeasts. Tioconazole exhibits fungicidal activity in vitro against Candida albicans, other species of the genus Candida, and against Torulopsis glabrata. Tioconazole prevents the growth and function of some fungal organisms by interfering with the production of substances needed to preserve the cell membrane. This drug is effective only for infections caused by fungal organisms. It will not work for bacterial or viral infections.

Tioconazole interacts with 14-a demethylase, a cytochrome P-450 enzyme that converts lanosterol to ergosterol, an essential component of the yeast membrane. In this way, tioconazole inhibits ergosterol synthesis, resulting in increased cellular permeability. Tioconazole may also inhibit endogenous respiration, interact with membrane phospholipids, inhibit the transformation of yeasts to mycelial forms and the uptake of purine, impair triglyceride and/or phospholipid biosynthesis, and inhibit the movement of calcium and potassium ions across the cell membrane by blocking the ion transport pathway known as the Gardos channel.

Tioconazole, 1-[2-{(2-chloro-3-thienyl) methoxy}-2(2, 4-dichlorophenyl) ethyl] 1, H-imidazole, is a topical antifungal agent. Its chemical formula is C16H13Cl3N2OS with a molecular weight of 387.7 g/mo. It has a structural formula of:

US 4,062,966 A discloses Tioconazole product.

US 5,529,782 A discloses a device adapted for local administration of an agent material in an internal body area such as the vagina, rectum, oral cavity, nasal passages and the like, comprises a dissolvable element and an agent material carried in said dissolvable element, wherein said dissolvable element is made of dissolvable polymer material, particularly, a mixture of polyvinyl alcohol, polyethylene oxide, and/or complex carbohydrate material, which are selected such that the dissolvable element remains in solid form before use, and dissolves due to human body temperatures and moisture during use to release said agent material for local administration in the internal body area.

US 7,939,098 B2 discloses a transmucosal composition for delivery of an active pharmaceutically acceptable agent through nasal, buccal or vaginal mucosa, said composition consisting essentially of about 0.01 to about 60%, preferably from about 5 to about 20%, of ethoxydiglycol or another non-ionizable glycol, said composition formulated as a solution, suspension, emulsion, gel, lotion, spray, tablet, dissolvable tablet for buccal use, ointment or foam for administration thereof alone or incorporated into a device for insertion into nasal, buccal or vaginal cavity.

WO 2005/013906 A2 discloses a pH-responsive film comprising: (a) a biocompatible, hydrophilic polymer that is positively charged at a first pH and in electronically neutral form at a higher pH; and (b) an alkylene oxide polymer or copolymer.

WO 2009/043588 A2 discloses antibacterial films that may regulate pH and control bacterial growth in the oral or vaginal environment and methods of use thereof. The films may include Lactic acid as pH adjusting ingredient, eucalyptus oil, menthol, peppermint oil, crisp mint oil, spearmint oil, Pelargonium sidoides root extract as antimicrobial essential oil, and polyvinyl alcohol, polyethylene glycol, and rice starch as polymer. The polymer may include polyvinyl alcohol, polyethylene glycol, and rice starch. The vaginal films and methods of use may treat infections in the vagina.

Natalia L. Calvo et al., Int J Pharm 2019 Feb 10:556:181-191 discloses vaginal films based on chitosan, hydroxypropyl methylcellulose and blends of these polymers containing tioconazole, were developed and thoroughly characterized to improve the conventional therapeutics of vaginal candidiasis.

Natalia L. Calvo et al., Journal of Pharmaceutical and Biomedical Analysis 205 (2021) 114303 discloses a new tioconazole (TCZ) mucoadhesive film, based on a biodegradable chitosan/ hydroxypropyl methylcellulose (CH/HPMC) blend, was developed for treatment of vaginal candidiasis. The formulation was optimized through an I-optimal design (minimizing the integral of the prediction variance across the factor space), where the impact of the proportion of the ingredients and processing variables on the quality of the final product was evaluated. Both, the thickness of the film and the swelling index, which affect patients’ comfort and compliance, were considered.

However, chitosan causes cytotoxicity and further chitosan is not soluble in the water. To solubilize the chitosan organic solvents such as acetic acid (1%) have to be used. The use of acetic acid increases the manufacturing cost of the product. To avoid the cytotoxicity and solubility issue of chitosan in water, and to reduce the overall manufacturing cost of Tioconazole vaginal films of the present invention avoids usage of chitosan as film former.

None of the prior-art disclosed the Tioconazole vaginal film composition of the present application. The inventors of present invention have developed specific Tioconazole vaginal film composition. The present invention has developed using combination of two mucoadhesive film formers such as Hypromellose and Poly vinyl alcohol and polyvinyl pyrrolidone (k 90) as dissolution enhancer/solubilizing agent. The inventors of present invention have also developed specific process for the preparation of Tioconazole vaginal film.

The Tioconazole vaginal film of the present invention us stable, safe and effective finished dosage form and it is developed based on the use of novel vaginal film technology.
OBJECTIVE OF INVENTION
The main objective of the present invention is to provide a pharmaceutical composition of Tioconazole.

Another objective of the present invention is to provide a pharmaceutical composition of Tioconazole vaginal film.

Another objective of the present invention is to provide a pharmaceutical composition of Tioconazole vaginal film comprising Tioconazole and pharmaceutically acceptable excipients.

Another objective of the present invention is to provide a pharmaceutical composition of Tioconazole vaginal film comprising Tioconazole and pharmaceutically acceptable excipients selected from film-forming agents, solubilizing agents, plasticizers, Opacifier and solvents.

Yet another objective of the present invention is to provide a process for the preparation of Tioconazole vaginal film.

SUMMARY OF INVENTION
Accordingly, the present invention provides a pharmaceutical composition of Tioconazole.

In one embodiment, the present invention provides a pharmaceutical composition of Tioconazole vaginal film.

In one embodiment, the present invention provides a pharmaceutical composition of Tioconazole vaginal film comprising Tioconazole and pharmaceutically acceptable excipients.

In one embodiment, the present invention provides a pharmaceutical composition of Tioconazole vaginal film comprising Tioconazole and pharmaceutically acceptable excipients selected from film-forming agents, solubilizing agents, plasticizers, Opacifiers and solvents.

In another embodiment, the present invention provides process for the preparation of Tioconazole vaginal film.

In yet another embodiment, the present invention is to provide a pharmaceutical composition of Tioconazole vaginal film comprising:
a) 10 to 60 % w/w of Active ingredient,
b) 10 to 70 % w/w of Film forming agents,
c) 1 to 10 % w/w of solubilizing agents,
d) 1 to 20 % w/w of Plasticizers,
e) 0.1 to 5 % w/w of Opacifiers, and
f) Solvents qs.

Yet another embodiment of the present invention provides a pharmaceutical composition of Tioconazole vaginal film comprising:
a) 10 to 60 % w/w of Tioconazole,
b) 1 to 10 % w/w of polyvinyl pyrrolidone,
c) 1 to 50 % w/w of hydroxypropylmethylcellulose,
d) 1 to 50 % w/w of polyvinyl alcohol,
e) 1 to 10 % w/w of glycerine,
f) 1 to 10 % w/w of propylene glycol,
g) 0.1 to 5 % w/w of titanium dioxide, and
h) solvents in qs.

Yet another embodiment of the present invention provides a process for the preparation of Tioconazole vaginal film.

Yet another embodiment of the present invention provides a process for the preparation of Tioconazole vaginal film, wherein the process comprising steps of:
a) adding film forming agents to solvent under stirring to get viscous dispersion,
b) adding plasticizers to solvent and mixing to get the clear solution,
c) adding Tioconazole to step (b) solution and mixing to get clear solution,
d) adding Opacifier in solvent and mixing to get uniform dispersion,
e) adding dispersion of step (d) to step (e) solution and mixing the final polymeric dispersion,
f) deaerating polymeric drug dispersion prepared in step (e) by applying vacuum,
g) coating the polymeric drug dispersion obtained in step (f) and drying in hot air oven, and
h) cutting the film role into desired size using slitter and packing the films into suitable pouches.

Yet another embodiment of the present invention provides a process for the preparation of Tioconazole vaginal film, wherein the process comprising steps of:
a) adding polyvinyl alcohol under stirring, polyvinyl pyrrolidone in purifies water and mixing to get viscous dispersion,
b) heating the dispersion to get uniform viscous dispersion,
c) adding hydroxypropylmethylcellulose and mixing up to form uniform viscous hazy dispersion and cooling the solution,
d) adding propylene glycol and glycerine to acetone and mixing to get the clear solution,
e) adding Tioconazole to step (d) solution and mixing to get clear solution,
f) adding titanium dioxide in purified water and mixing to get uniform dispersion,
g) adding dispersion of step (f) to step (d) solution and mixing the final polymeric dispersion,
h) deaerating Polymeric drug dispersion prepared in step (g) by applying vacuum,
i) coating the polymeric drug dispersion obtained in step (h) and drying in hot air oven, and
j) cutting the film role into desired size using slitter and packing the films into suitable pouches.

DETAILED DESCRIPTION OF THE INVENTION
The term "comprising", which is synonymous with "including", "containing", or "characterized by" here is defined as being inclusive or open-ended, and does not exclude additional, unrecited elements or method steps, unless the context clearly requires otherwise.

Accordingly, the present invention provides a pharmaceutical composition of Tioconazole.

In one embodiment, the present invention provides a pharmaceutical composition of Tioconazole vaginal film.

In one embodiment, the present invention provides a pharmaceutical composition of Tioconazole vaginal film comprising Tioconazole and pharmaceutically acceptable excipients.

In one embodiment, the present invention provides a pharmaceutical composition of Tioconazole vaginal film comprising Tioconazole and pharmaceutically acceptable excipients selected from film-forming polymers, solubilizing agent, plasticizers, Opacifiers and solvents.

In another embodiment, the present invention provides a process for the preparation of Tioconazole vaginal film.

The vaginal films pharmaceutical form consists of a thin and small sheet of polymeric hydrophilic substances that disperse or dissolve in contact with vaginal fluids to release the active substance. Vaginal films are pharmaceutical forms that are convenient, discrete, they do not require the use of an applicator to be administered and, as they disperse in vaginal fluids, they have low risk of increasing fluids volume and leak out, therefore improving comfort of use and efficacy after administration. Other advantages of vaginal films include their portability and low cost per unit. Since they are solid pharmaceutical forms, films can vehicle drugs that are susceptible to hydrolytic degradation, guaranteeing their stability. They can be formulated for immediate or sustained drug release.

The term “vaginal film” of the present invention can be interchangeably used with “vaginal device”.

The term “active ingredient” of the present invention is used to treats fungal and yeast infections. Topical formulations are used for ringworm, jock itch, athlete's foot, and tinea versicolor or "sun fungus".

Preferably used active ingredient is Tioconazole. The concentration of Tioconazole used in the vaginal film is from 10 to 60 % w/w in total weight of the composition.

Tioconazole is a broad-spectrum imidazole antifungal agent that inhibits the growth of human pathogenic yeasts. Tioconazole exhibits fungicidal activity in vitro against Candida albicans, other species of the genus Candida, and against Torulopsis glabrata. Tioconazole prevents the growth and function of some fungal organisms by interfering with the production of substances needed to preserve the cell membrane. This drug is effective only for infections caused by fungal organisms. It will not work for bacterial or viral infections.

The term “film forming agents” as used herein includes but not limited to hydroxyethyl cellulose, carrageen, eudragit EPO, hydroxypropyl cellulose, hydroxypropylmethylcellulose, gums, starch, polymerized rosin, pullulan, sodium alginate, pectin, gelatine, chitosan, maltodextrins, polyvinyl alcohol, sodium carboxy methyl cellulose, copovidone, polyvinyl pyrrolidone, poloxamer.

The concentration of film forming agents used in the composition of the present invention is from 10 to 70 % w/w of the total weight of the composition.

The solubilizing agent can be selected from polyvinylpyrrolidones, polyvinylcaprolactam-polyvinylacetate-polyethyleneglycol copolymer, Polyoxyl 40 Hydrogenated Castor Oil / Macrogol glycerol Hydroxystearate, fatty acids, castor oil, cyclodextrins, polyethyleneglycol, glyceryl distearate, lecithin, monoglycerides, diglycerides, triglycerides, propylene glycol monostearate, Labrafils (e.g., oleoyl macrogol-6 glycerides, oleoyl polyoxyl-6-glycerides, linoleoyl macrogol-6 glycerides, linoleoyl polyoxyl-6 glycerides, lauroyl macrogol-6 glycerides, lauroyl polyoxyl-6 glycerides), Labrasols (e.g., caprylocaproyl macrogol-8 glycerides, caprylocaproyl polyoxyl-8 glycerides), Solutols (e.g., poly-oxyethylene esters of 12-hydroxystearic acid), Soluplus (e.g., polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft co-polymer), derivatives thereof,

The concentration of solubilizing agent used in the composition of the present invention is from 1 to 10 % w/w of the total weight of the composition.

Plasticizers are low molecular weight compounds that can be added to the formulation to increase the plasticity, soften the polymer carrier, and enhance the flexibility of the final product. The addition of plasticizers to the formulation can improve the manufacturing conditions or the physiochemical properties of the film.

Plasticizers used in the composition of the present invention include but not limited to triacetin, low molecular weight polyethylene glycols, triethyl citrate, glycerine, propylene glycol and vitamin E TPGS.

Propylene glycol and glycerin were used as plasticizer and hygroscopic material to prevent moisture loss.

The concentration of plasticizers used in the composition of the present invention is from 1 to 20% w/w of the total weight of the composition.

Opacifier used in the composition of the present invention include but not limited to titanium dioxide.

The concentration of Opacifier used in the composition of the present invention is from 0.1 to 5 % w/w of the total weight of the composition.

Colorants used in the composition of the present invention include but not limited to titanium dioxide, FD&C, D&C, lakes and any approved colour/colorants.

The concentration of colorants used in the composition of the present invention is from 0.1 to 5 % w/w of the total weight of the composition.

The solvents used in the present invention are water, a polar organic solvent including, but not limited to, ethanol, isopropanol, acetone, methylene chloride, or any combination thereof.

The composition of present invention may also contain other excipients such as lubricants, disintegrating agents, preservatives and other conventionally using excipients.

Lubricants used in the composition of the present invention include but not limited to stearic acid, magnesium stearate, calcium stearate, sodium lauryl sulphate, hydrogenated vegetable oil, hydrogenated castor oil, sodium stearyl fumarate, macrogols, or mixtures thereof.

Disintegrants used in the composition of the present invention include but not limited to croscarmellose sodium, alginic acid, carboxymethylcellulose, carboxymethylcellulose sodium, hydroxypropylcellulose (low substituted), microcrystalline cellulose, powdered cellulose, crospovidone, methylcellulose, polacrilin potassium, sodium alginate, sodium starch glycolate, starch, disodium disulfite, disodium edathamil, disodium edetate, disodiumethylenediaminetetraacetate (EDTA) crosslinked polyvinylpyrollidines, pregelatinized starch, carboxymethyl starch, sodium carboxymethyl starch, microcrystalline cellulose. Preferably, the disintegrants used in the solid oral composition is of one or more disintegrants includes crosscarmelose sodium and sodium starch glycolate.

Preservatives used in the composition of the present invention include but not limited to parabens such as methyl paraben, propyl paraben, benzyl alcohol, sodium benzoate, phenol, benzalkonium chloride, thimerosal, chlorobutanol, benzoic acid, sodium bisulfite, and sodium proprionate. Preferably, the preservative used in the solid oral composition is methyl paraben.

The present invention is illustrated in detail but not limiting to, the following examples. It will be apparent to those skilled in the art that many modifications may be practiced without departing from the scope of the invention.

EXAMPLE 1
S. No Name of the Material Quantity per film
mg %w/w
1 Tioconazole USP 300.00 43.48
2 Polyvinyl Pyrrolidone (K 90) IP 30.00 4.35
3 Glycerine IP 19.00 2.75
4 Hydroxypropyl Methylcellulose 15 CPS USP 120.00 17.39
5 Polyvinyl Alcohol Cold WS (160000 MW) IP 150.00 24.64
6 Propylene Glycol IP 50.00 7.25
7 Titanium Dioxide IP 1.00 0.14
8 Acetone IH 400.00** --
9 Purified Water IP 1666.00** --
Total Weight 671.00 100.00
** Acetone and purified water evaporated during the drying process and did not appeal in finished product except in traces.

Manufacturing Process
Preparation of Polymeric Solution
Transferred 90% of batch quantity of purified water to SS vessel. Added batch quantity of polyvinyl alcohol under stirring and added batch quantity of polyvinyl pyrrolidone K-90 and mixed up to get viscous dispersion free from lumps and heat up to reach temperature 80 ± 50C mix up to form uniform viscous dispersion. Added batch quantity of Hydroxypropyl methyl cellulose mixed up to form uniform viscous hazy dispersion then cooled down polymeric solution to 20 to 250C.

Preparation of Tioconazole Dispersion
Transferred 10% of batch quantity of Acetone to another SS vessel. Added batch quantity of propylene glycol and mixed for 5 min using stirrer. Added batch quantity of glycerine and mixed for 5 min using stirrer. Added 80% of batch quantity of Acetone solution and mixed up to get clear solution. Added batch quantity of Tioconazole to and mixed for 5 min and apply heat 400C ± 20C until clear solution was formed. Added this clear solution to polymeric solution and mixed for 20 min using stirrer. Rinsed the SS vessel with 10% batch quantity of acetone and added the rinses to main manufacturing vessel under stirring. 2% of Purified water taken in another beaker and to this added titanium dioxide and mixed for 5 min (Or) until uniform dispersion obtained. Added this dispersion to main polymeric solution and mixed for 10 min. rinsed the manufacturing vessel with 8% batch quantity of purified water and added the rinses to main vessel. Then mixed the final polymeric dispersion for 50-60 minutes using stirrer.

De-aeration:
Polymeric drug dispersion prepared was subjected to de-aeration by applying vacuum.

Coating & drying:
The polymeric drug dispersion was coated on polyester and dried in hot air oven chambers at 800c.

Slitting:
Dried mother roll is cut into a desired size using slitter.

Packing
Packed the film into suitable pouches.

Example 2
S. No Name of the Material Quantity per film
mg %w/w
1 Tioconazole USP 300.00 52.54
2 Polyvinyl Pyrrolidone (K 90) IP 30.00 5.25
3 Hydroxypropyl Methylcellulose 15 CPS USP 120.00 21.01
4 Polyvinyl Alcohol Cold WS (160000 MW) IP 100 17.51
5 Propylene Glycol IP 20.00 3.50
6 Titanium Dioxide IP 1.00 0.18
7 Acetone IH 200.00** --
8 Purified Water IP 1200.00** --
Total Weight 571.00 100.00
** Acetone and purified water evaporated during the drying process and did not appeal in finished product except in traces.

Manufacturing Process
Preparation of Polymeric Solution
Transferred 90% of batch quantity of purified water to SS vessel. Added batch quantity of polyvinyl alcohol under stirring and added batch quantity of polyvinyl pyrrolidone K-90 and mixed up to get viscous dispersion free from lumps and heat up to reach temperature 80 ± 50C mix up to form uniform dispersion. Added Hydroxypropyl methyl cellulose mixed up to form uniform dispersion then cooled down polymeric solution.

Preparation of Tioconazole Dispersion
Transferred 10% of batch quantity of Acetone to another SS vessel. Added batch quantity of propylene glycol and mixed for 5 min using stirrer. Added Tioconazole to and mixed for 5 min and apply heat 400C ± 20C until clear solution was formed. Added this clear solution to polymeric solution and mixed for 20 min using stirrer. Added titanium dioxide dispersion into this solution.

De-aeration:
Polymeric drug dispersion prepared was subjected to de-aeration by applying vacuum.

Coating & drying:
The polymeric drug dispersion was coated on polyester and dried in hot air oven chambers.

Slitting:
Dried mother roll is cut into a desired size using slitter.

Packing
Packed the film into suitable pouches.

Example 3
S. No Name of the Material Quantity per film
mg %w/w
1 Tioconazole USP 300.00 48.31
2 Polyvinyl Pyrrolidone (K 90) IP 30.00 4.83
3 Hydroxypropyl Methylcellulose 15 CPS USP 120.00 19.32
4 Polyvinyl Alcohol Cold WS (160000 MW) IP 150 24.15
5 Propylene Glycol IP 20.00 3.22
6 Titanium Dioxide IP 1.00 0.16
7 Acetone IH 200.00** --
8 Purified Water IP 1400.00** --
Total Weight 621.00 100.00
**Acetone and purified water evaporated during the drying process and did not appeal in finished product except in traces.

Manufacturing Process
Preparation of Polymeric Solution
Transferred 90% of batch quantity of purified water to SS vessel. Added batch quantity of polyvinyl alcohol under stirring and added batch quantity of polyvinyl pyrrolidone K-90 and mixed up to get viscous dispersion free from lumps and heat up to reach temperature 80 ± 50C mix up to form uniform dispersion. Added Hydroxypropyl methyl cellulose mixed up to form uniform dispersion then cooled down polymeric solution.

Preparation of Tioconazole Dispersion
Transferred 10% of batch quantity of Acetone to another SS vessel. Added batch quantity of propylene glycol and mixed for 5 min using stirrer. Added Tioconazole to and mixed for 5 min and apply heat 400C ± 20C until clear solution was formed. Added this clear solution to polymeric solution and mixed for 20 min using stirrer. Added titanium dioxide dispersion into this solution.

De-aeration:
Polymeric drug dispersion prepared was subjected to de-aeration by applying vacuum.

Coating & drying:
The polymeric drug dispersion was coated on polyester and dried in hot air oven chambers.

Slitting:
Dried mother roll is cut into a desired size using slitter.

Packing
Packed the film into suitable pouches.

Example 4
S. No Name of the Material Quantity per film
mg %w/w
1 Tioconazole USP 300.00* 44.12
2 Polyoxyl 40 Hydrogenated Castor Oil / Macrogolglycerol Hydroxystearate 20.00 2.94
3 Glycerine IP 19.00 2.79
4 Hydroxypropyl Methylcellulose 15 CPS USP 120.00** 17.65
5 Polyvinyl Alcohol Cold WS (160000 MW) IP 150.00 25.00
6 Propylene Glycol IP 50.00 7.35
7 Titanium Dioxide IP 1.00 0.15
8 Acetone IH Q.S** --
9 Purified Water IP Q.S** --
Total Weight 680.00 100.00
**Acetone and purified water evaporated during the drying process and did not appeal in finished product except in traces.

Manufacturing Process
Preparation of Polymeric Solution
Transferred 90% of batch quantity of purified water to SS vessel. Added batch quantity of polyvinyl alcohol under stirring and added batch quantity of Polyoxyl 40 Hydrogenated Castor Oil / Macrogolglycerol Hydroxystearate and mixed up to get viscous dispersion free from lumps and heat up to reach temperature 80 ± 50C mix up to form uniform viscous dispersion. Added batch quantity of Hydroxypropyl methyl cellulose mixed up to form uniform viscous hazy dispersion then cooled down polymeric solution to 20 to 250C.

Preparation of Tioconazole Dispersion
Transferred 10% of batch quantity of Acetone to another SS vessel. Added batch quantity of propylene glycol and mixed for 5 min using stirrer. Added batch quantity of glycerine and mixed for 5 min using stirrer. Added 80% of batch quantity of Acetone solution and mixed up to get clear solution. Added batch quantity of Tioconazole to and mixed for 5 min and apply heat 400C ± 20C until clear solution was formed. Added this clear solution to polymeric solution and mixed for 20 min using stirrer. Rinsed the SS vessel with 10% batch quantity of acetone and added the rinses to main manufacturing vessel under stirring. 2% of Purified water taken in another beaker and to this added titanium dioxide and mixed for 5 min (Or) until uniform dispersion obtained. Added this dispersion to main polymeric solution and mixed for 10 min. rinsed the manufacturing vessel with 8% batch quantity of purified water and added the rinses to main vessel. Then mixed the final polymeric dispersion for 50-60 minutes using stirrer.

De-aeration:
Polymeric drug dispersion prepared was subjected to de-aeration by applying vacuum.

Coating & drying:
The polymeric drug dispersion was coated on polyester and dried in hot air oven chambers at 800c.

Slitting:
Dried mother roll is cut into a desired size using slitter.

Example 5:
S. No Name of the Material Quantity per film
mg %w/w
1 Tioconazole USP 300.00* 43.48
2 Polyoxyl 40 Hydrogenated Castor Oil / Macrogolglycerol Hydroxystearate 20.00 2.90
3 Polyvinyl Pyrrolidone (K 90) IP
10.00 1.45
4 Glycerine IP 19.00 2.75
5 Hydroxypropyl Methylcellulose 15 CPS USP 120.00** 17.39
6 Polyvinyl Alcohol Cold WS (160000 MW) IP 150.00 24.64
7 Propylene Glycol IP 50.00 7.25
8 Titanium Dioxide IP 1.00 0.14
9 Acetone IH Q.S** --
10 Purified Water IP Q.S** --
Total Weight 690.00 100.00

Manufacturing Process
Preparation of Polymeric Solution
Transferred 90% of batch quantity of purified water to SS vessel. Added batch quantity of polyvinyl alcohol under stirring and added batch quantity of Polyoxyl 40 Hydrogenated Castor Oil / Macrogolglycerol Hydroxystearate and Polyvinyl Pyrrolidone (K 90) and mixed up to get viscous dispersion free from lumps and heat up to reach temperature 80 ± 50C mix up to form uniform viscous dispersion. Added batch quantity of Hydroxypropyl methyl cellulose mixed up to form uniform viscous hazy dispersion then cooled down polymeric solution to 20 to 250C.

Preparation of Tioconazole Dispersion
Transferred 10% of batch quantity of Acetone to another SS vessel. Added batch quantity of propylene glycol and mixed for 5 min using stirrer. Added batch quantity of glycerine and mixed for 5 min using stirrer. Added 80% of batch quantity of Acetone solution and mixed up to get clear solution. Added batch quantity of Tioconazole to and mixed for 5 min and apply heat 400C ± 20C until clear solution was formed. Added this clear solution to polymeric solution and mixed for 20 min using stirrer. Rinsed the SS vessel with 10% batch quantity of acetone and added the rinses to main manufacturing vessel under stirring. 2% of Purified water taken in another beaker and to this added titanium dioxide and mixed for 5 min (Or) until uniform dispersion obtained. Added this dispersion to main polymeric solution and mixed for 10 min. rinsed the manufacturing vessel with 8% batch quantity of purified water and added the rinses to main vessel. Then mixed the final polymeric dispersion for 50-60 minutes using stirrer.

De-aeration:
Polymeric drug dispersion prepared was subjected to de-aeration by applying vacuum.

Coating & drying:
The polymeric drug dispersion was coated on polyester and dried in hot air oven chambers at 800c.

Slitting:
Dried mother roll is cut into a desired size using slitter.

Example 6:
S. No Name of the Material Quantity per film
mg %w/w
1 Tioconazole USP 300.00* 43.48
2 Polyvinyl Pyrrolidone (K 90) IP
30.00 4.35
3 Glycerine IP 19.00 2.17
4 Triethyl citrate 4.00 0.58
5 Hydroxypropyl Methylcellulose 15 CPS USP 120.00** 17.39
6 Polyvinyl Alcohol Cold WS (160000 MW) IP 150.00 24.64
7 Propylene Glycol IP 50.00 7.25
8 Titanium Dioxide IP 1.00 0.14
9 Acetone IH Q.S** --
10 Purified Water IP Q.S** --
Total Weight 690.00 100.00

Manufacturing Process
Preparation of Polymeric Solution
Transferred 90% of batch quantity of purified water to SS vessel. Added batch quantity of polyvinyl alcohol under stirring and added batch quantity of Polyviny Pyrrolidone (K 90) and mixed up to get viscous dispersion free from lumps and heat up to reach temperature 80 ± 50C mix up to form uniform viscous dispersion. Added batch quantity of Hydroxypropyl methyl cellulose mixed up to form uniform viscous hazy dispersion then cooled down polymeric solution to 20 to 250C.

Preparation of Tioconazole Dispersion
Transferred 10% of batch quantity of Acetone to another SS vessel. Added batch quantity of propylene glycol and mixed for 5 min using stirrer. Added batch quantity of glycerine and mixed for 5 min using stirrer. Added batch quantity of Triethyl citrate and mixed for 5 min using stirrer Added 80% of batch quantity of Acetone solution and mixed up to get clear solution. Added batch quantity of Tioconazole to and mixed for 5 min and apply heat 400C ± 20C until clear solution was formed. Added this clear solution to polymeric solution and mixed for 20 min using stirrer. Rinsed the SS vessel with 10% batch quantity of acetone and added the rinses to main manufacturing vessel under stirring. 2% of Purified water taken in another beaker and to this added titanium dioxide and mixed for 5 min (Or) until uniform dispersion is obtained. Added this dispersion to main polymeric solution and mixed for 10 min. rinsed the manufacturing vessel with 8% batch quantity of purified water and added the rinses to main vessel. Then mixed the final polymeric dispersion for 50-60 minutes using stirrer.

De-aeration:
Polymeric drug dispersion prepared was subjected to de-aeration by applying vacuum.

Coating & drying:
The polymeric drug dispersion was coated on polyester and dried in hot air oven chambers at 800c.

Slitting:
Dried mother roll is cut into a desired size using slitter.

Example 7:
S. No Name of the Material Quantity per film
mg %w/w
1 Tioconazole USP 300.00* 50.00
2 Polyvinyl Pyrrolidone (K 90) IP
30.00 5.00
3 Polyvinyl Alcohol Cold WS (160000 MW) IP 280.00** 46.67
4 Propylene Glycol IP 69.00 11.50
5 Titanium Dioxide IP 1.00 0.14
6 Acetone IH Q.S** --
7 Purified Water IP Q.S** --
Total Weight 690.00 100.00

Manufacturing Process
Preparation of Polymeric Solution
Transferred 90% of batch quantity of purified water to SS vessel. Added batch quantity of polyvinyl alcohol under stirring and added batch quantity of Polyvinyl Pyrrolidone (K 90) and mixed up to get viscous dispersion free from lumps and heat up to reach temperature 80 ± 50C mix up to form uniform viscous dispersion, then cooled down polymeric solution to 20 to 250C.

Preparation of Tioconazole Dispersion
Transferred 10% of batch quantity of Acetone to another SS vessel. Added batch quantity of propylene glycol and mixed for 5 min using stirrer. Added batch quantity of glycerine and mixed for 5 min using stirrer. Added 80% of batch quantity of Acetone solution and mixed up to get clear solution. Added batch quantity of Tioconazole to and mixed for 5 min and apply heat 400C ± 20C until clear solution was formed. Added this clear solution to polymeric solution and mixed for 20 min using stirrer. Rinsed the SS vessel with 10% batch quantity of acetone and added the rinses to main manufacturing vessel under stirring. 2% of Purified water taken in another beaker and to this added titanium dioxide and mixed for 5 min (Or) until uniform dispersion is obtained. Added this dispersion to main polymeric solution and mixed for 10 min. rinsed the manufacturing vessel with 8% batch quantity of purified water and added the rinses to main vessel. Then mixed the final polymeric dispersion for 50-60 minutes using stirrer.

De-aeration:
Polymeric drug dispersion prepared was subjected to de-aeration by applying vacuum.

Coating & drying:
The polymeric drug dispersion was coated on polyester and dried in hot air oven chambers at 800c.

Slitting:
Dried mother roll is cut into a desired size using slitter.

Example 8:
S. No Name of the Material Quantity per film
mg %w/w
1 Tioconazole USP 300.00* 50.00
2 Polyvinyl Pyrrolidone (K 90) IP
30.00 5.00
3 Hydroxypropyl Methylcellulose 15 CPS USP 280.00** 46.67
4 Propylene Glycol IP 69.00 11.50
5 Titanium Dioxide IP 1.00 0.14
6 Acetone IH Q.S** --
7 Purified Water IP Q.S** --
Total Weight 690.00 100.00

Manufacturing Process
Preparation of Polymeric Solution
Transferred 90% of batch quantity of purified water to SS vessel. Added batch quantity Polyviny Pyrrolidone (K 90) and mixed up to get viscous dispersion free from lumps and heat up to reach temperature 80 ± 50C mix up to form uniform viscous dispersion. Added batch quantity of Hydroxypropyl methyl cellulose mixed up to form uniform viscous hazy dispersion then cooled down polymeric solution to 20 to 250C.

Preparation of Tioconazole Dispersion
Transferred 10% of batch quantity of Acetone to another SS vessel. Added batch quantity of propylene glycol and mixed for 5 min using stirrer. Added 80% of batch quantity of Acetone solution and mixed up to get clear solution. Added batch quantity of Tioconazole to and mixed for 5 min and apply heat 400C ± 20C until clear solution was formed. Added this clear solution to polymeric solution and mixed for 20 min using stirrer. Rinsed the SS vessel with 10% batch quantity of acetone and added the rinses to main manufacturing vessel under stirring. 2% of Purified water taken in another beaker and to this added titanium dioxide and mixed for 5 min (Or) until uniform dispersion is obtained. Added this dispersion to main polymeric solution and mixed for 10 min. rinsed the manufacturing vessel with 8% batch quantity of purified water and added the rinses to main vessel. Then mixed the final polymeric dispersion for 50-60 minutes using stirrer.

De-aeration:
Polymeric drug dispersion prepared was subjected to de-aeration by applying vacuum.

Coating & drying:
The polymeric drug dispersion was coated on polyester and dried in hot air oven chambers at 800c.

Slitting:
Dried mother roll is cut into a desired size using slitter.

Example 9:
S. No Name of the Material Quantity per film
mg %w/w
1 Tioconazole USP 300.00* 45.05

2 Polyvinyl Pyrrolidone (K 90) IP 30.00 4.50

3 Polyvinyl Alcohol Cold WS (160000 MW) 280.00** 42.04

4 Glycerol 55.00 8.26

5 Titanium Dioxide IP 1.00 0.15

6 Acetone IH Q.S** --
7 Purified Water IP Q.S** --
Total Weight 690.00 100.00

Manufacturing Process
Preparation of Polymeric Solution
Transferred 90% of batch quantity of purified water to SS vessel. Added batch quantity of polyvinyl alcohol under stirring and added batch quantity of Polyvinyl Pyrrolidone (K 90) and mixed up to get viscous dispersion free from lumps and heat up to reach temperature 80 ± 50C mix up to form uniform viscous dispersion, then cooled down polymeric solution to 20 to 250C.

Preparation of Tioconazole Dispersion
Transferred 10% of batch quantity of Acetone to another SS vessel. Added batch quantity of Glycerine/Glycerol and mixed for 5 min using stirrer. Added batch quantity of glycerine and mixed for 5 min using stirrer. Added 80% of batch quantity of Acetone solution and mixed up to get clear solution. Added batch quantity of Tioconazole to and mixed for 5 min and apply heat 400C ± 20C until clear solution was formed. Added this clear solution to polymeric solution and mixed for 20 min using stirrer. Rinsed the SS vessel with 10% batch quantity of acetone and added the rinses to main manufacturing vessel under stirring. 2% of Purified water taken in another beaker and to this added titanium dioxide and mixed for 5 min (Or) until uniform dispersion is obtained. Added this dispersion to main polymeric solution and mixed for 10 min. rinsed the manufacturing vessel with 8% batch quantity of purified water and added the rinses to main vessel. Then mixed the final polymeric dispersion for 50-60 minutes using stirrer.

De-aeration:
Polymeric drug dispersion prepared was subjected to de-aeration by applying vacuum.

Coating & drying:
The polymeric drug dispersion was coated on polyester and dried in hot air oven chambers at 800c.

Slitting:
Dried mother roll is cut into a desired size using slitter.

Example 10:
S. No Name of the Material Quantity per film
mg %w/w
1 Tioconazole USP 300.00* 45.05

2 Polyvinyl Pyrrolidone (K 90) 30.00 4.50

3 Hydroxypropyl Methylcellulose 15 CPS 280.00** 42.04

4 Glycerin IP 69.00 8.26

5 Titanium Dioxide IP 1.00 0.15

6 Acetone IH Q.S** --
7 Purified Water IP Q.S** --
Total Weight 690.00 100.00

Manufacturing Process
Preparation of Polymeric Solution
Transferred 90% of batch quantity of purified water to SS vessel. Added batch quantity Polyviny Pyrrolidone (K 90) and mixed up to get viscous dispersion free from lumps and heat up to reach temperature 80 ± 50C mix up to form uniform viscous dispersion. Added batch quantity of Hydroxypropyl methyl cellulose mixed up to form uniform viscous hazy dispersion then cooled down polymeric solution to 20 to 250C.

Preparation of Tioconazole Dispersion
Transferred 10% of batch quantity of Acetone to another SS vessel. Added batch quantity of glycerin and mixed for 5 min using stirrer. Added 80% of batch quantity of Acetone solution and mixed up to get clear solution. Added batch quantity of Tioconazole to and mixed for 5 min and apply heat 400C ± 20C until clear solution was formed. Added this clear solution to polymeric solution and mixed for 20 min using stirrer. Rinsed the SS vessel with 10% batch quantity of acetone and added the rinses to main manufacturing vessel under stirring. 2% of Purified water taken in another beaker and to this added titanium dioxide and mixed for 5 min (Or) until uniform dispersion is obtained. Added this dispersion to main polymeric solution and mixed for 10 min. rinsed the manufacturing vessel with 8% batch quantity of purified water and added the rinses to main vessel. Then mixed the final polymeric dispersion for 50-60 minutes using stirrer.

De-aeration:
Polymeric drug dispersion prepared was subjected to de-aeration by applying vacuum.

Coating & drying:
The polymeric drug dispersion was coated on polyester and dried in hot air oven chambers at 800c.

Slitting:
Dried mother roll is cut into a desired size using slitter.

The product of present invention has evaluated for various physicochemical properties like water content, disintegration time, dissolution, assay, related substances and microbial limits.

The stability data at various stability conditions 40°C ± 2°C/75%± 5% RH, 30°C ± 2°C/75% ± 5% RH, 25°C ± 2°C/60% ± 5% RH. The data depicted below in the table
Stability Data of Validation Batch - 40°C ± 2°C/75%± 5% RH
S. No Parameter Specification Initial 1M 2M 3M 6M
1 Description White colored opaque square shaped, vaginal film Complies Complies Complies Complies Complies
2 Water content (w/w) NMT 10.0 % 7.48 7.49 6.93 7.00 6.97
3 Disintegration time (min) NMT 300 sec 200 205 195 211 210
4 Dissolution (%)
Film -1

NLT 80% in 45mins
98.6 101.1 98.5 111.2 101.7
Film -2 95.3 101.6 104.3 97.7 101.6
Film -3 98.7 103.1 103.2 99.6 99.0
Film -4 98.2 101.1 99.1 94.8 98.8
Film -5 95.1 101.8 100.2 101.9 101.4
Film -6 95.1 102.6 103.2 106.3 103.8
Average 96.9 101.9 101.4 101.9 101.1
5 Assay (%) NLT 90.0 & NMT 110.0 (w/w) 99.6 98.1 99.8 98.9 97.2
6 Related Substances (%)
Impurity -A NMT 2.0 ND ND ND ND ND
Impurity -B NMT 2.0 ND ND ND ND ND
Impurity -C NMT 2.0 0.01 0.03 0.004 0.02 0.02
Unknown Impurity NMT 1.0 BDL BDL BDL BDL BDL
Total Impurity NMT 2.0 0.01 0.03 0.004 0.02 0.02
7 Total Aerobic viable count
Total Aerobic Microbial count NMT 100cfu/g 15 CFU/g -- -- -- 15 CFU/g
Total Combined Yeasts and Molds Count NMT 100cfu/g Complies -- -- -- Complies
Tests For Specific Microorganisms
Candida albicans Should be absent in 1 Absent -- -- -- Absent
Staphylococcus aureus Should be absent in 1 Absent -- -- -- Absent
Pseudomonas aeruginosa Should be absent in 1 Absent -- -- -- Absent
Summary and conclusion: All the test results are complying up to 6 month accelerated condition as per stability specification; ND: Not Detected, BDL: Below Disregard Limit

Stability Data: 30°C ± 2°C/75% ± 5% RH
S. No Parameter Specification Initial 3M 6M 9M
1 Description White colored opaque square shaped, vaginal film Complies Complies Complies Complies
2 Water content (w/w) NMT 10.0 % 7.48 7.29 6.29 6.53
3 Disintegration time (min) NMT 300 sec 200 202 203 193

4 Dissolution (%)
Film -1

NLT 80% in 45mins
98.6 109.1 101.6 100.4
Film -2 95.3 97.9 102.2 90.6
Film -3 98.7 99.9 99.0 99.9
Film -4 98.2 94.9 98.9 98.7
Film -5 95.1 101.9 101.3 100.1
Film -6 95.1 106.5 103.5 99.5
Average 96.9 102.0 101.1 98.2
5 Assay (%) NLT 90.0 & NMT 110.0 (w/w) 99.6 99.6 97.6 96.4
6 Related Substances (%)
Impurity -A NMT 0.2% ND ND ND ND
Impurity -B NMT 0.2% ND ND ND ND
Impurity -C NMT 0.2% 0.01 0.02 0.02 0.03
Unknown Impurity NMT 0.2% BDL BDL BDL BDL
Total Impurity NMT 1.0% 0.01 0.02 0.02 0.03
7 Total Aerobic viable count
Total Aerobic Microbial count NMT 100cfu/g 15 cfu/g -- -- --
Total Combined Yeasts and Molds Count NMT 100cfu/g Complies -- -- --
Tests For Specific Microorganisms
Candida albicans Should be absent in 1 Absent -- -- --
Staphylococcus aureus Should be absent in 1 Absent -- -- --
Pseudomonas aeruginosa Should be absent in 1 Absent -- -- --
Summary and conclusion: All the test results are complying up to 9 months as per stability specification; ND: Not Detected, BDL: Below Disregard Limit

Stability Data: 25°C ± 2°C/60% ± 5% RH
S. No Parameter Specification Initial 3M 6M 9M
1 Description White colored opaque square shaped, vaginal film Complies Complies Complies Complies
2 Water content (w/w) NMT 10.0 % 7.48 7.23 6.97 6.63
3 Disintegration time (min) NMT 300 sec 200 207 209 192

4 Dissolution (%)
Film -1

NLT 80% in 45mins
98.6 110.6 103.4 100.2
Film -2 95.3 109.9 101.7 90.6
Film -3 98.7 93.4 102.8 97.5
Film -4 98.2 93.5 98.9 102.0
Film -5 95.1 93.9 101.7 100.1
Film -6 95.1 93.7 101.3 98.8
Average 96.8 99.2 101.6 98.2
5 Assay (%) NLT 90.0 & NMT 110.0 (w/w) 99.6 97.4 97.5 97.7
6 Related Substances (%)
Impurity -A NMT 2.0 ND ND ND ND
Impurity -B NMT 2.0 ND ND ND ND
Impurity -C NMT 2.0 0.01 0.02 0.02 0.03
Unknown Impurity NMT 1.0 BDL BDL BDL BDL
Total Impurity NMT 2.0 0.01 0.02 0.02 0.03
7 Total Aerobic viable count
Total Aerobic Microbial count NMT 100cfu/g 15 cfu/g -- -- --
Total Combined Yeasts and Molds Count NMT 100cfu/g Complies -- -- --
Tests For Specific Microorganisms
Candida albicans Should be absent in 1 Absent -- -- --
Staphylococcus aureus Should be absent in 1 Absent -- -- --
Pseudomonas aeruginosa Should be absent in 1 Absent -- -- --
Summary and conclusion: All the test results are complying up to 9 months as per stability specification; ND: Not Detected, BDL: Below Disregard Limit

As per the data provided in above tables, the composition of the present invention has passed all the physico chemical tests.

Characteristics of Vaginal film:
a. Hydrophilic to lipophilic polymers matric system.
b. Disintegrates within 120 to 180 seconds.Thickness of the film ranges from 100 to 150 microns.
c. Surface area ranges from 1 to 20 square centimeters.
d. No leakage.
e. Longer residence time of formulation as its bio-adhesive.
f. Flexible thin film.

Advantages of Dosage form:

a. Applicator not required.
b. Economical compared to creams with applicators.
c. The film quickly dissolves to form bioadhesive gel after insertion and releases the drug.
d. Easy to use, so improved patient acceptability.
e. No messiness.
f. Ease of handling during manufacturing and transportation.
g. Faster release and rapid onset of action.
h. Precise dose delivery compared t0 vaginal cream/gel/lotion.

,CLAIMS:

WE CLAIM

1. A pharmaceutical composition of Tioconazole vaginal film comprising Tioconazole and pharmaceutically acceptable excipients, wherein the Tioconazole present in the range from 10 to 60 % w/w in total weight of the composition.

2. The composition as claimed in claim 1, wherein pharmaceutically acceptable excipients selected from film-forming agents, solubilizing agents, plasticizers, Opacifiers and solvents.

3. The composition as claimed in claim 2, wherein film forming agents are selected from hydroxyethyl cellulose, carrageen, eudragit EPO, hydroxypropyl cellulose, hydroxypropylmethylcellulose, gums, starch, polymerized rosin, pullulan, sodium alginate, pectin, gelatine, chitosan, maltodextrins, polyvinyl alcohol, sodium carboxy methyl cellulose, copovidone, polyvinyl pyrrolidone, poloxamer, the concentration of film forming agents is from 10 to 70 % w/w of the total weight of the composition.

4. The composition as claimed in claim 2, wherein solubilizing agent selected from polyvinylpyrrolidones, polyvinylcaprolactam-polyvinylacetate-polyethyleneglycol copolymer, Polyoxyl 40 Hydrogenated Castor Oil / Macrogol glycerol Hydroxystearate, fatty acids, castor oil, cyclodextrins, polyethyleneglycol, glyceryl distearate, lecithin, monoglycerides, diglycerides, triglycerides, propylene glycol monostearate, Labrafils (e.g., oleoyl macrogol-6 glycerides, oleoyl polyoxyl-6-glycerides, linoleoyl macrogol-6 glycerides, linoleoyl polyoxyl-6 glycerides, lauroyl macrogol-6 glycerides, lauroyl polyoxyl-6 glycerides), Labrasols (e.g., caprylocaproyl macrogol-8 glycerides, caprylocaproyl polyoxyl-8 glycerides), Solutols (e.g., poly-oxyethylene esters of 12-hydroxystearic acid), Soluplus (e.g., polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft co-polymer), derivatives thereof, the concentration of solubilizing agent is from 1 to 10 % w/w of the total weight of the composition.

5. The composition as claimed in claim 2, wherein plasticizers are selected from triacetin, low molecular weight polyethylene glycols, triethyl citrate, glycerine, propylene glycol and vitamin E TPGS, the concentration of plasticizers is from 1 to 20% w/w of the total weight of the composition.

6. The composition as claimed in claim 2, wherein Opacifiers are selected from titanium dioxide, the concentration of Opacifiers is from 0.1 to 5 % w/w of the total weight of the composition.

7. The composition as claimed in claim 2, wherein the solvents are selected from ethanol, isopropanol, acetone, methylene chloride, or any combination thereof.

8. The composition as claimed in claim 1, the composition further comprising excipients selected from lubricants, disintegrating agents, preservatives and other conventionally using excipients.

9. The process for the preparation of Tioconazole vaginal film as claimed in claim 1, wherein the process comprising steps of:
a) adding film forming agents to solvent under stirring to get viscous dispersion,
b) adding plasticizers to solvent and mixing to get the clear solution,
c) adding Tioconazole to step (b) solution and mixing to get clear solution,
d) adding Opacifier in solvent and mixing to get uniform dispersion,
e) adding dispersion of step (d) to step (e) solution and mixing the final polymeric dispersion,
f) deaerating polymeric drug dispersion prepared in step (e) by applying vacuum,
g) coating the polymeric drug dispersion obtained in step (f) and drying in hot air oven, and
h) cutting the film role into desired size using slitter and packing the films into suitable pouches.

Dated this Eighteenth (18th) day of March, 2025

_________________________________
Dr. S. Padmaja
Agent for the Applicant
IN/PA/883