FORM 2
THE PATENT ACT 1970
(39 of 1970)
&
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10 and rulel3)
1. TITLE OF THE INVENTION:
RAPID DISSOLVING, TASTE MASKED THIN FILM CONTAINING SILDENAFIL
2. APPLICANT (S):
(a) NAME: AJANTA PHARMA LIMITED.
(b) NATIONALITY: INDIAN
(c) ADDRESS: Ajanta House, Charkop, Kandivali (West),
Mumbai-400 067.
3. COMPLETE:
The following specification particularly describes the invention and the manner in
which is to be performed.

Field of the Invention:
The present invention discloses a composition containing effective dose of Sildenafil or its isomers, enantiomers, pharmaceutically acceptable salts thereof, in the form of rapid dissolving thin film, wherein the bitter taste of Sildenafil has been masked by forming a Sildenafil mask complex with Polyacrylic Resin.
Background of the Invention:
Sildenafil, chemically l-[[3-(4,7-Dihydro-l-methyl-7-oxo-3-propyl-lH-
pyrazolo[4,3-d]pyrimidin-5-yl)-4-ethoxyphenyl]sulfonyl]-4-methylpiperazine; is a selective phosphodiesterase type 5 inhibitor. Sildenafil and its salts are well known for treatment of male erectile dysfunction.
Sildenafil is available in different dosage forms, such as. tablets, capsules, pills. However, solid dosage forms, which are administered orally, need to be swallowed whole or chewed to deliver medication with adequate amounts of liquid. Some patients, particularly geriatric, may have difficulty in swallowing or chewing such dosage forms. The administration of sildenafil may benefit from the presentation of a fast dissolving dosage form. However, sildenafil citrate has a very strong bitter taste, which renders the administration of fast dissolving dosage form of Sildenafil an unpleasant experience.
US Patent Nos. 5,948,430 and 6,552,024 discloses mucoadhesive film compositions. However, the film described in these patents relies on the use of at least one surfactant.
Several formulations and dosage forms are known in prior art. WO 00/07596 discloses a pharmaceutical formulation which can be rapidly dissolved in water and which, as an active constituent, contains the phosphodiesterase (PDE) type 5 inhibitor sildenafil or the pharmaceutically safe salts thereof.
US application US 2006100214 discloses fast dissolving and taste masked dosage form comprising sildenafil granules and solubilisation inhibitor. In the claimed

dosage form, the bitterness of the Sildenafil was masked with solubilisation inhibitor.
US Patent No. 6531114 discloses chewing gum formulation for delivering a sildenafil citrate. However, this method will have uncontrolled rale and extent of drug delivery that seriously varies the drug efficacy.
WO 04/087111 assigned to Ranbaxy discloses oral taste masked pharmaceutical compositions that include a core having an active ingredient coated with a mixture of polymeric film forming binders and inorganic carriers. Also provided are processes for preparing the oral taste masked pharmaceutical composition.
WO 04/022037 assigned to Ranbaxy relates to taste masked dosage forms utilizing low amounts of taste masking polymer, and simple and economical processes for the preparation of the taste masked dosage forms. The taste-masked dosage form includes one or more drugs and one or more cationic polymers synthesized from dimethylaminoethyl methacrylate and neutral methacrylic acid esters. The wt/wt ratio of the drug to polymer is less than about one to two.
US Application 2006/0159758 relates to coating compositions for taste masking and methods for applying the coating compositions to dosage forms to mask the taste of a medicinal substance. The taste masking coating compositions generally include a copolymer of acrylate and methacrylate with a quaternary ammonium group in combination with sodium carboxymethylcellulose and a polyvinyl alcohol-polyethylene glycol copolymer.
US application 20090047330 discloses oral fast dissolving films for erectile dysfunction bioactive agents wherein the bitter taste of the Sildenafil has been masked by p-cyclodextrin derivatives.
There is a need for an effective pharmaceutical dosage form incorporating a sildenafil salt that dissolves rapidly within the oral cavity, has a pleasant mouthfeel without the bitter taste and does not require complicated manufacturing processes.

Object of the Invention:
The object of the present invention is to provide a pharmaceutical composition containing Sildenafil in the form of rapid dissolving, taste masked thin film having pleasant mouthfeel without the bitter taste.
Summary of the Invention:
While working on the problems associated with prior art. the present inventors have found out the pharmaceutical composition containing Sildenafil or salts thereof in the form of rapid dissolving thin film, in which the bitter taste of the Sildenafil has been masked by forming a Sildenafil mask complex.
Detailed Description of the Invention:
According to first particular aspect of the invention there is provided a pharmaceutical composition in the form of rapidly dissolving, taste masked thin film containing Sildenafil or its isomers, enantiomers. pharmaceutically acceptable salts thereof which may adhere to the oral mucosa thereby releasing the active agent.
According to another aspect of the invention there is provided a pharmaceutical composition in the form of rapidly dissolving, taste masked thin film containing Sildenafil or its isomers, enantiomers, pharmaceutically acceptable salts thereof and one or more polyacrylic resin.
According to another aspect of the invention there is provided a pharmaceutical composition in the form of rapidly dissolving, taste masked thin film containing Sildenafil or its isomers, enantiomers, pharmaceutically acceptable salts thereof and one or more polyacrylic resin where in a cationic exchange occurs.
According to yet another aspect of the invention there is provided a pharmaceutical composition in the form of rapidly dissolving, taste masked thin film comprising Sildenafil or its isomers, enantiomers. pharmaceutically acceptable salts thereof,

one or more polyacrylic resin and optionally one or more pharmaceutically acceptable excipients.
According to yet another aspect of the invention there is provided a pharmaceutical composition in the form of rapidly dissolving, taste masked thin film comprising Sildenafil or its isomers, enantiomers, pharmaceutically acceptable salts thereof, one or more polyacrylic resin and optionally one or more polyalcohols, sweetening agents, thickening or gelling agents, colorants, flavors, flavor enhancers.
According to yet another aspect of the invention there is provided a process for the preparation of pharmaceutical composition in the form of rapidly dissolving, taste masked thin film comprising Sildenafil or its isomers, enantiomers. pharmaceutically acceptable salts thereof, one or more polyacrylic resin and optionally one or more pharmaceutically acceptable excipients.
According to yet another aspect of the invention there is provided a process for the preparation of pharmaceutical composition in the form of rapidly dissolving, taste masked thin film comprising Sildenafil or its isomers, enantiomers, pharmaceutically acceptable salts thereof, one or more polyacrylic resin and optionally one or more polyalcohols, sweetening agents, thickening or gelling agents, colorants, flavors, flavor enhancers.
According to another aspect of the invention there is provided a pharmaceutical composition in the form of rapidly dissolving, taste masked thin film comprising Sildenafil or its isomers, enantiomers. pharmaceutically acceptable salts thereof and one or more polyacrylic resin, wherein the said film is substantially free from surfactant and p-cyclodextrin derivatives.
There is a commercially available product by the name InstamaskR [IC-MK-9014 White] and sold by Ideal Cures Pvt. Ltd., India. The ready mix comprises of a polyacrylic resin which is cationic in nature. In addition it comprises carbomer and powdered cellulose. The polyacrylic resin does not belong to the class of methacrylic acid esters. It has free binding sites wherein the sildenafil citrate gets

exchanged. Sildenafil Citrate forms a complex with polyacrylic resins by simple anion exchange mechanism resulting in Sildenafil complexing with Polyacrylic resin and in the process releasing sodium citrate in the filtrate. The pure Sildenafil -Resin complex is collected and dried and used in the process.
In another general aspect there is provided a process for the preparation of an oral, taste masked, rapid dissolving composition of sildenafil citrate using an ion-exchange mechanism to mask the bitter taste of the drug. The process includes forming a mask complex of sildenafil citrate by using Instacoat MK 9014 by using an aqueous process to obtain taste masked granules which are suitably sized followed by aqueous granulation of the masked complex with various excipients and then lubrication of the final mass before compression into tablets using suitable tooling.
According to another aspect of the invention, the solvent used in the said process is selected from isopropyl alcohol, methylene chloride or mixture thereof.
In another aspect of the invention, there is provided a process for the preparation of a rapidly dissolving, taste masked thin film of Sildenafil comprising the steps of
a) preparing Sildenafil mask complex by reacting Sildenafil or its isomers, enantiomers, pharmaceutically acceptable salts thereof with polyacrylic resin,
b) optionally adding one or more pharmaceutical!)' acceptable excipients,
c) adding one or more suitable solvents to form a slurry,
d) pouring the slurry in strip moulds and
e) drying at suitable temperature to form a film.
In another aspect of the invention, there is provided a process for the preparation of a rapidly dissolving, taste masked thin film of Sildenafil comprising the steps of
a) preparing Sildenafil mask complex by reacting Sildenafil or its isomers, enantiomers, pharmaceutically acceptable salts thereof with Instacoat MK 9014,
b) optionally adding one or more pharmaceutically acceptable excipients,

c) adding one or more suitable solvents to form a slurry.
d) pouring the slurry in strip moulds and
e) drying at suitable temperature to form a film.
The dry film may be cut into pieces of suitable size and shape and packed into suitable container as per the requirement and convenience.
"Pharmaceutically acceptable excipient" means an excipient that is useful in preparing a pharmaceutical composition that is generally safe, non-toxic, and desirable.
The polyalcohol used in the present composition comprises of xylitol. sucralose. glycerol, polyethlene glycol, propylene glycol, glycerol monoesters with fatty acids or other pharmaceutically acceptable polyalcohols or mixtures thereof.
The sweetening agents are selected from sugar, dextrose, lactose, mannilol. sucrose, xylitol, malitol, acesulfame potassium, talin. glycyrrhizin. sucralose. aspartame, saccharin, sodium saccharin, sodium cyclamate, honey or mixtures thereof.
Thickening or gelling agents that may be added in the film are selected from, but not limited to Locust bean gum. carrageenen or mixtures thereof. Preferably, the thickening agent or mixture of thickening agent is to be added in 0.8 - 3.2% with respect to total weight of composition.
The flavors which may be added optionally in the composition are selected from the essential oils or water soluble extracts of menthol, wintergreen, peppermint, sweet mint, spearmint, vanillin, cherry, chocolate, cinnamon, clove, lemon, orange. raspberry, rose, spice, violet, herbal, fruit, strawberry, grape, pineapple, peach. kiwi, papaya, mango, coconut, apple, coffee, plum, watermelon, nuts, durean. green tea, grapefruit, banana, butter, camomile. The effect of flavors may be enhanced using flavor enhancers like tartaric acid, citric acid, vanillin, or the like.

Preferably, the flavour or mixture of flavours is to be added in 8.2 - 32% with respect to total weight of composition.
Colorants which may optionally be mixed in the film must be safe in terms of toxicity and should be accepted by the Food and Drug Administration for use in pharmaceutical and cosmetic compositions.
According to another aspect of the invention, the drying temperature in the said process is maintained below the boiling point of the solvent employed in the said process. The drying temperature range varies from 10 to 100 °C, preferably 25 to 60 °C.
Example 1
Procedure for the preparation of Sildenafil Citrate mask complex:
The mixture of Instacoat MK 9014 and water was stirred for 30 minutes. The equal quantity of Sildenafil Citrate to that of Instacoat MK 9014 was added and stirred again to get uniform dispersibility. After two hours of stirring, centrifuge the mass and dry the solid product at 60o C to get granules of the Sildenafil Citrate mask complex.
Procedure for the preparation of thin film:
Sildenafil Citrate mask complex and Menthol were sifted through sieve no. 60 and mixed for 10 minutes. This mixture is then mixed with Xylitol, Sucralose, Citric acid monohydrate. Loctus Bean Gum, Carrageenan and Hypromellose. This mixture was stirred well for 10 minutes. Polyethylene Glycol was added with continuous stirring to form a paste. Then, Peppermint KAL 427, Isopropyl alcohol and Methylene chloride were added to get uniform, homogenous viscous fluid. Finally, Quinoline yellow and brilliant blue were added and stirred for 15 minutes. The slurry was poured in strip moulds by using semiautomatic liquid filling machine and dried at about 40 °C up to 10 hours. The dried strips were wrapped in Aluminium lined paper.

Table 1
Composition Quantity per strip in mg Quantity (% on dry
weight basis)
Sildenafil Mask Complex* 280.96 25.541
Xylitol 250.00 22.727
Sucralose 100.00 9.090
Citric acid monohydrate 50.00 4.545
Menthol 0.92 0.0836
Locust bean gum 9.00 0.820
Carrageenan 9.00 0.820
HPMC(MethocelE-15) 80.00 7.272
lsopropyl alcohol Q.S.
Methylene chloride Q.S. -
Polyethylene glycol 400 230.00 20.909
Peppermint KAL 427 90.00 8.200
Quinoline yellow WS 0.06 0.005
Brilliant Blue FCF 0.06 0.005
Total Weight of strip 1100.00 100.00

*280.96mg of Sildenafil Cit of Sildenafil Citrate equivale rate mask compl nt 100mg Sild ex contains i40.480mg enafil

Example 2
Procedure for the preparation of Sildenafil Citrate mask complex and procedure for the preparation of thin film were followed as given in Example 1.
Table 2
Composition Quantity per strip in mg Quantity (%on dry
weight basis) J
Sildenafil Mask Complex* 280.96 25.541
Xylitol 259.24 23.568
Sucralose 100.00 9.090
Citric acid monohydrate 50.00 4.545
Menthol 0.92 0.0836
Locust bean gum 4.4 0.40
Carrageenan 4.4 0.40
HPMC(MethocelE-15) 80.00 7.272
Isopropyl alcohol Q.S. -
Methylene chloride Q.S. -
Polyethylene glycol 400 230.00 20.909
Peppermint KAL 427 90.00 8.200
Quinoline yellow WS 0.06 0.005
Brilliant Blue FCF . 0.06 0.005
Total Weight of strip 1100.00 100.00

* 280.96mg of Sildenafil Citrate mask complex contains I40.480mg of Sildenafil Citrate equivalent to 100mg Sildenafil

Example 3
Procedure for the preparation of Sildenafil Citrate mask complex and procedure for the preparation of thin film were followed as given in Example 1
Table 3
Composition Quantity per strip in mg Quantity (% on dry weight basis)
Sildenafil Mask Complex* 280.96 25.541
Xylitol 232.83 21.167
Sucralose 100.00 9.090
Citric acid monohydrate 50.00 4.545
Menthol 0.92 0.0836
Locust bean gum 17.6 1.60
Carrageenan 17.6 1.60
HPMC(MethocelE-15) 80.00 7.272
Isopropyl alcohol Q.S. -
Methylene chloride Q.S. -
Polyethylene glycol 400 230.00 20.909
Peppermint KAL 427 90.00 8.200
Quinoline yellow WS 0.06 0.005
Brilliant Blue FCF 0.06 0.005
Total Weight of strip 1100.00 100.00

* 280.96mg of Sildenafil Citrate mask complex contains I40.480mg of Sildenafil Citrate equivalent to 100mg Sildenafil

I Claim,
1) A pharmaceutical composition in the form of rapidly dissolving, taste masked thin film comprising Sildenafil or its isomers, enantiomers, pharmaceutically acceptable salts thereof and one or more polyacrylic resins.
2) A pharmaceutical composition in the form of rapidly dissolving, taste masked thin film comprising Sildenafil or its isomers, enantiomers, pharmaceutically acceptable salts thereof, one or more polyacrylic resins and optionally one or more pharmaceutically acceptable excipients.
3) A pharmaceutical composition in the form of rapidly dissolving, taste masked thin film comprising Sildenafil or its isomers, enantiomers. pharmaceutically acceptable salts thereof, one or more polyacrylic resin, polyalcohols. sweetening agents, thickening or gelling agents, colorants, flavors, flavor enhancers and mixture thereof.
4) The polyaicohol as claimed in claim 3 comprises of xylitol, sucralose. glycerol. polyethlene glycol, propylene glycol, glycerol monoesters with fatty acids or mixtures thereof.
5) The sweetening agents as claimed in claim 3 comprises of sugar, dextrose, lactose, mannitol, sucrose, xylitol, malitol, acesulfame potassium, talin, glycyrrhizin, sucralose, aspartame, saccharin, sodium saccharin, sodium cyclamate, honey or mixtures thereof.
6) The Thickening or gelling agents as claimed in claim 3 comprises of Locust bean gum. carrageenen or mixtures thereof.
7) The thickening agent as claimed in claim 6 is added in range 0.8 - 3.2% with respect to total weight of composition.
8) A process for the preparation of pharmaceutical composition in the form of rapidly dissolving, taste masked thin film comprising Sildenafil or its isomers. enantiomers, pharmaceutically acceptable salts thereof, one or more polyacrylic resins and optionally one or more pharmaceutically acceptable excipients.
9) A process for the preparation of a rapidly dissolving, taste masked thin film of Sildenafil comprising the steps of

a) preparing Sildenafil mask complex by reacting Sildenafil or its isomers, enantiomers, pharmaceutically acceptable salts thereof with polyacrylic resins.
b) optionally adding one or more pharmaceutically acceptable excipients,
c) adding one or more suitable solvents to form a slurry.
d) pouring the slurry in strip moulds and
e) drying at suitable temperature to form a film.
10) A process for the preparation of a rapidly dissolving, taste masked thin film of Sildenafil comprising the steps of
a) preparing Sildenafil mask complex by reacting Sildenafil or its isomers, enantiomers, pharmaceutically acceptable salts thereof with Instacoat MK 9014,
b) optionally adding one or more pharmaceutically acceptable excipients,
c) adding one or more suitable solvents to form a slurry,
d) pouring the slurry in strip moulds, and
e) drying at suitable temperature to form a film.