FIELD OF THE INVENTION
The present invention relates to the taste masked orally dissolving strips comprising Sildenafil Citrate and the process for preparation thereof.
BACKGROUND OF THE INVENTION
Sildenafil Citrate is a selective inhibitor of cyclic guanosine monophosphate (cGMP)  specific phosphodiesterase type 5 (PDE-5)  commercially developed by Pfizer  Inc. as VIAGRA®. Sildenafil Citrate is designated chemically as 1-[[3-(6  7-dihydro-1-methyl-7-oxo-3-propyl-1Hpyrazolo [4  3-d] pyrimidin-5-yl)-4-ethoxyphenyl] sulfonyl]-4 methyl piperazine citrate and has the following structure 

Sildenafil Citrate is a white to off-white crystalline powder with a solubility of 3.5 mg/ml in water and has the molecular weight of 666.7. The physiologic mechanism of erection of the penis involves release of nitric oxide in the corpus cavernosum during sexual stimulation. Nitric oxide then activates the enzyme guanylate cyclase  which results in increased levels of cyclic guanosine monophosphate (cGMP)  producing smooth muscle relaxation in the corpus cavernosum and allowing the inflow of blood. Sildenafil Citrate has no direct relaxant effect on isolated human corpus cavernosum  but enhances the effect of nitric oxide by inhibiting phosphodiesterase type 5  which is responsible for degradation of cGMP in the corpus cavernosum. When sexual stimulation causes local release of nitric oxide  inhibition of PDE-5 by Sildenafil Citrate causes increased levels of cGMP in the corpus cavernosum  resulting in smooth muscle relaxation and inflow of blood to the corpus cavernosum. Sildenafil Citrate at recommended doses has no effect in the absence of sexual stimulation.
However Sildenafil Citrate has a very bitter taste and hence tablets such as Viagra®  which are commercially available are film coated. The film coating masks any bitter taste in the mouth and these tablets have to be taken with water  which makes it difficult to administer. To overcome the difficulties of administering the film coated tablets of Sildenafil Citrate with water  and to mask the bitter taste of Sildenafil citrate  different taste masked oral formulations that can be easily disintegrated in the oral cavity without water are described in the prior art.
WO2004017976A1 describes the fast dissolving and taste masked Sildenafil citrate solid dosage form that has a pleasant mouth feel comprising Sildenafil Citrate granules  which granules comprise a Solubilization inhibitor for the Sildenafil Citrate  and optionally a sweetening agent and one or more disintegrants.
WO2009074995A1 describes the taste masked chewable taste masked compositions of Sildenafil Citrate comprising a therapeutically effective amount of Sildenafil Citrate or a pharmaceutically acceptable derivative thereof  in the form of Sildenafil citrate mask complex formed by Sildenafil and a polyacrylic resin by a cationic exchange mechanism.
WO2011030351A1 describes the taste masked pharmaceutical tablets compositions of PDE-5 inhibitors comprising at least one PDE-5 inhibitor  at least one taste masking agent and at least one pharmaceutically excipient.
The prior art does not disclose the taste masked orally dissolving strips of Sildenafil citrate  that remain in contact with taste receptors in mouth for a longer period of time  that can be easily disintegrated in the oral cavity without water  just by the action of saliva. Therefore the present invention discloses the taste masked orally dissolving strips of Sildenafil citrate that comprise Sildenafil citrate and a taste masking agent that disintegrate in less than 30 seconds in the oral cavity.
SUMMARY OF THE INVENTION
One embodiment of the present invention relates to the taste masked orally dissolving strips of Sildenafil citrate comprising Sildenafil citrate  a taste masking agent and at least one pharmaceutically acceptable excipient wherein the taste masked orally dissolving strips of sildenafil citrate disintegrates in less than 30 seconds in the oral cavity.
Another embodiment of the present invention relates to the taste masked orally dissolving strips of Sildenafil citrate comprising Sildenafil citrate  a taste masking agent  a film forming agent  Disintegrant  and optionally plasticizing agent  sweetening agents  flavoring agents and colorants wherein the taste masked orally dissolving strips of sildenafil citrate disintegrates in less than 30 seconds in the oral cavity.
Another embodiment of the present invention relates to the process for the preparation of the taste masked orally dissolving strips of Sildenafil Citrate by i) dissolving the film forming agent in the purified water  ii) dispersing the Sildenafil citrate  taste masking polymer  Disintegrant  flavoring agents and sweetening agents in the purified water  iii) combining the materials of steps i  and ii  iv) adding the plasticizing agent to step iii  followed by colorant v) to forming the strip of the materials in step iv on the polyester roll  vi) drying the film formed in step v and vii) manually cutting the dried strips and packing the taste masked orally dissolving strips of Sildenafil Citrate.

DETAILED DESCRIPTION OF THE INVENTION
Reference will now be made in detail to the presently preferred embodiments of the invention  which  together with the following examples  serve to explain the principles of the invention. These embodiments are described in sufficient detail to enable those skilled in the art to practice the invention  and it is to be understood that other embodiments may be utilized  and that various structural  biological and chemical changes may be made without departing from the spirit and scope of the present invention.
The present invention relates to the taste masked orally dissolving strips of Sildenafil citrate comprising Sildenafil citrate as the active ingredient  a taste masking agent and other pharmaceutically acceptable excipients  wherein the taste masked orally dissolving strips of sildenafil citrate disintegrates in less than 30 seconds in the oral cavity.
The suitable taste masking agents that are used in the tasted masked orally dissolving strips of Sildenafil citrate are selected from the group of suitable cationic exchange resin that include Amberlite ® IRP64 (porous copolymer of methacrylic acid and divinylbenzene)  Amberlite ® IRP69 (sulfonated copolymer of styrene and divinylbenzene)  Amberlite ® IRP88 (cross linked polymer of methacrylic acid and divinylbenzene)  DOWEX ® RTM. resins (strong cationic exchangers based upon polystyrenesulphonic acid with variable cross linking (1-12% divinylbenzene)  Tulsion ® 335 - (Polacrilex/Polacirilex S)  Tulsion ®-339 (Polacrilin potassium USP)  Tulsion ® 344 (Sodium polystyrene sulfonate BP)  Indion ® 204 (crosslinked polyacrylic acid)  Indion ® 214 (crosslinked polyacrylic acid)  Indion ® 234 (crosslinked polyacrylic acid)  Indion ® 234S (crosslinked polyacrylic acid)  Indion ® 294 (crosslinked polyacrylic acid)  Purolite ® C115 HMR (carboxylic acid functional group)  Purolite ® C1 5 E (carboxylic acid functional group)  Purolite ® C100 HMR (sulfonic acid functional group)  Purolite ® 100 MR (sulfonic acid functional group) or cation exchange resins having phosphonic functioned groups and the like or any combinations thereof. The preferred cation exchange resin used in the taste masked orally dissolving strips of Sildenafil Citrate is Polacrilin potassium (Tulsion ®339). In one embodiment  ion exchange resin can be used for complexation with Sildenafil citrate is in a ratio of active to resin of about 1:0.1 to about 1:3.
Another embodiment of the present invention relates to the taste masked orally dissolving strips of Sildenafil citrate comprising Sildenafil citrate  a taste masking agent  a film forming agent  Disintegrant  and optionally plasticizing agent  sweetening agents  flavoring agents and colorants  wherein the taste masked orally dissolving strips of Sildenafil Citrate disintegrates in less than 30 seconds in the oral cavity.
The suitable film forming agents is the water soluble polymer film forming material which is a pharmaceutically acceptable polymer selected from the following categories including synthetic and natural polymer material. These can include polyanionic  polycationic and uncharged polymer species including Cellulose polymers (synthetic) such as Hydroxypropylmethyl cellulose (HPMC)  Hydroxy propyl cellulose (HPC)  Methyl Cellulose (MC)  Carboxymethyl cellulose (CMC)  Starches  and Cellulose polymers (natural) such as Acacia  Tragacanth  Carrageenan  Pullulan and Other water soluble polymers including Polystyrene sulfonates  Polyethylene oxides/Polyethylene glycols  Polyacrylic acids  Polybenzenesulfonic acids  Polyethylenimine  Poly diallyldimethyl ammonium chloride  Polyallylamine hydrochloride  Polyvinyl pyrrolidone (PVP) and Gelatin. The water soluble polymeric materials also can be pectin and derivatives  guar gum  xanthan gum  gellan sodium salt  propyleneglycol alginate  starches (amylose  amylopectin)  modified starches  hydroxyethyl starch  pullulan  carboxymethyl starch  gum ghatti  okra gum  karaya gum  dextrans  dextrins and maltodextrins  konjac  acemannan from aloe  locust bean gum  tara gum  quince seed gum  fenugreek seed gum  scleroglucan  gum arabic  psyllium seed gum  tamarind gum  oat gum  quince seed gum  carrageenans  scleraglucan  succinoglucan  larch arabinogalactan  flaxseed gum  chondroitin sulfates  hyaluronic acid  curdlan  chitosan  deacetylated konjac  and rhizobium gum. The preferred film forming agent in the preparation of the taste masked orally dissolving strips is hydroxypropylmethyl cellulose. The hydroxypropylmethyl cellulose ranges from about 10% to 30% w/w of the taste masked orally dissolving strip of sildenafil citrate.
The suitable plasticizing agents are selected from glycerol  triethyl citrate  triacetin  polyethylene glycols etc. The preferred plasticizing agent glycerol  triethyl citrate or mixture thereof. The amount of plasticizer is present in the amount of 0.1-25% w/w of the taste masked orally dissolving strip of Sildenafil Citrate.
The suitable Disintegrants are selected from crospovidione  Croscarmellose sodium  sodium starch glycollate and pregelatinized starch. The preferred Disintegrant is Croscarmellose sodium.
Flavoring agents include 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  sugar  dextrose  lactose  mannitol  sucrose  xylitol  malitol  acesulfame potassium  talin  glycyrrhizin  sucralose  aspartame  saccharin  sodium saccharin  sodium cyclamate and honey.
The sweeteners may be chosen from the following non-limiting list: glucose (corn syrup)  dextrose  invert sugar  fructose  and combinations thereof; saccharin and its various salts such as the sodium salt; dipeptide sweeteners such as aspartame; dihydrochalcone compounds  glycyrrhizin; Stevia Rebaudiana (Stevioside); chloro derivatives of sucrose such as sucralose; sugar alcohols such as sorbitol  mannitol  xylitol  and the like. Also contemplated are hydrogenated starch hydrolysates and the synthetic sweetener 3 6-dihydro-6-methyl-1-1-1 2 3-oxathiazin-4-one-2 2-dioxide  particularly the potassium salt (acesulfame-K)  and sodium and calcium salts thereof.
Also color additives can be used in preparing the strips. A coloring agent  which may be provided in a dosage form of the present invention  includes pharmaceutically acceptable natural or artificially synthesized dyes. A great variety of such pharmaceutically acceptable dyes have been known to be suitable for use in pharmaceutical compositions  for example natural dyes such as annatto extract  anthocyanins  beta-carotene  beta APO 8  carotenal  black currant  burnt sugar  canthaxanthin  caramel  carbo medicinalis  carmine  carmine blue  carminic acid  carrot  brilliant blue FCF  chlorophyll  chlorophyllin  cochineal extract  copper-chlorophyll  copper-chlorophyllin  curcumin  curcumin/CU-chloro  elderberry  grape  hibiscus  lutein  mixed carotenoids  paprika  riboflavin  spinach  stinging nettle  titanium dioxide  turmeric  natural colors  aronia/redfruit  beet juice colors  paprika extract  paprika oleoresin; or artificial dyes such as allura red  amaranth  carmoisine  fast red E  erythrosine  green S  patent blue V  ponceau 4R  quinoline yellow  red 2G  sunset yellow  and tartrazine.
The following examples illustrate methods of preparing taste masking pharmaceutical orally dissolving strips in accordance with certain non-limiting aspects of the invention. All percentages in the examples are by weight unless otherwise indicated.
Example-1
Example-1: Taste masked orally dissolving strip 50mg
Composition per dosage unit
Component Composition Per Unit (%)
Sildenafil citrate 38
Polacrillin potassium 19
Sucralose 5
Vanilla flavor 2
Croscarmellose sodium 3
Hydroxy Propyl methyl cellulose 11
Triethyl citrate 10
Banana flavor 2
Polyethylene glycol 5
Glycerol 4.9
Brilliant blue 0.1
Purified water* Q.S
Total weight of dosage form 100

*present in traces in the final dosage unit

The process for the preparation of the taste masking orally dissolving strip of Sildenafil Citrate involves the following steps
1. Purified water was taken in a glass beaker  and then Polacrillin potassium is added to it and stirred for 10 minutes.
2. Sildenafil citrate was added to the contents of step 1 and stirred for 5 minutes.
3. Sucralose  Vanilla flavor and Croscarmellose sodium were added to the contents of step 2 and stirred for 10 minutes.
4. Hydorypropylmethylcellulose was added to the contents of step 3 and stirred for 5 minutes.
5. Glycerol  Triethyl citrate  Banana flavor  Polyethylene glycol and Brilliant blue were added to the contents of step 4 and stirred for 10 minutes.
6. The contents of the step 5 are layered on the polyethylene sheet and dried for 15 minutes at 90ºC  to form the orally dissolving strip of Sildenafil Citrate.
7. The above formed Strip in step 6 was cut into the desired sizes.

It will be seen that the objects set forth above  among those made apparent from the preceding description  are efficiently attained and  since certain changes may be made in carrying out the above process and composition set forth without departing from the spirit and scope of the invention is intended that all matter contained in the above description shall be interpreted as illustrated and not in a limiting sense.
It is also to be understood that the following claims are intended to cover all of the generic and specific features of the invention herein described and all statements of the scope of the invention in which  as a matter of language might be said to fall therebetween.

CLAIM
I claim

1. A taste masked orally dissolving strip of Sildenafil citrate comprising Sildenafil citrate as the active ingredient  a taste masking agent and other pharmaceutically acceptable excipients  wherein the taste masked orally dissolving strips of Sildenafil Citrate disintegrates in less than 30 seconds in the oral cavity.

2. The taste masked orally dissolving strip of Sildenafil citrate as claim 1 wherein the taste masking agent is Polacrilin potassium.

3. A taste masked orally dissolving strip of Sildenafil citrate comprising Sildenafil citrate  a taste masking agent  a film forming agent  Disintegrant  and optionally plasticizing agent  sweetening agents  flavoring agents and colorants  wherein the taste masked orally dissolving strips of sildenafil citrate disintegrates in less than 30 seconds in the oral cavity.

4. The taste masked orally dissolving strip of Sildenafil citrate as claim 3 wherein the taste masking agent is Polacrilin potassium.

5. The taste masked orally dissolving strip of Sildenafil citrate as claim 3 wherein the film forming agent is hydroxypropylmethyl cellulose.

6. The taste masked orally dissolving strip of Sildenafil citrate as claim 3 wherein the Disintegrant is Croscarmellose sodium.

7. The taste masked orally dissolving strip of Sildenafil citrate and the process thereof substantially as herein described with reference to any one of the embodiments of the invention illustrated in the accompanying examples.

Dated this 15th day of March 2012

SHRUTI KAUSHIK
AGENT FOR THE APPLICANT
IN/PA-1324