TASTE-MASKED ORAL FORMULATIONS OF INFLUENZA ANTIVIRALS

• US 20120093738A1
• Filed: 06/10/2010
• Published: 04/19/2012
• Est. Priority Date: 06/11/2009
• Status: Abandoned Application

• Current Assignee: Rubicon Research Pvt. Ltd.
• Original Assignee: Rubicon Research Pvt. Ltd.
• Inventors: Pilgaonkar, Pratibha Sudhir, Rustomjee, Maharukh Tehmasp, Gandhi, Anilkumar Surendrakumar
• Application Number:
  US13/377,740
• Publication Number:
  US 20120093738A1
• Time in Patent Office: Days
• US Class Current: 424/44
• CPC Class Codes: A61K 47/6951 using cyclodextrin cyclodextrins used as simple excipients A61K47/40
• CPC Class Codes: A61K 9/0056 Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
• CPC Class Codes: A61K 9/146 with organic macromolecular compounds
• CPC Class Codes: A61K 9/1617 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/1635 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/2027 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/2077 Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
• CPC Class Codes: A61K 9/2081 with microcapsules or coated microparticles according to A61K9/50
• CPC Class Codes: A61K 9/5015 Organic compounds, e.g. fats, sugars
• CPC Class Codes: A61K 9/5026 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/5047 Cellulose ethers containing no ester groups, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/5078 with drug-free core
• CPC Class Codes: A61P 31/16 for influenza or rhinoviruses
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery

Abstract

The present invention relates to taste-masked oral formulations of influenza antivirals. The taste-masked pharmaceutical formulations for oral administration comprise one or more influenza antivirals, at least one taste-masking agent and at least one pharmaceutically acceptable excipient. Further, the taste-masked influenza antiviral formulations of the present invention are provided in the form of dispersible tablets, effervescent tablets, orally disintegrating tablets, chewable tablets, bite-dispersion tablets or the like, wherein the bitter taste of influenza antivirals is masked thereby providing palatable formulations.

Claims

1. A taste-masked pharmaceutical formulation for oral administration comprising:

(a) at least one influenza antiviral;

(b) at least one taste-masking agent; and

(c) at least one pharmaceutically acceptable excipient.

2. The formulation of claim 1 wherein said influenza antiviral is oseltamivir, zanamivir, peramivir, amantadine or rimantadine in the form of a free base, a pharmaceutically acceptable salt, a prodrug, an active metabolite, a polymorph, a solvate, a hydrate, an enantiomer, an optical isomer, a tautomer or a racemic mixture thereof.

4. The formulation of claim 1 wherein said influenza antiviral is oseltamivir phosphate.

5. The formulation of claim 1 wherein said taste-masking agent is a polymeric pharmaceutically acceptable excipient, a non-polymeric pharmaceutically acceptable excipient, an adsorbent, a carbomer, an ion exchange resin, a sugar substitute, a cyclodextrin or a derivative thereof, or a combination thereof.

6. The formulation of claim 5 wherein said polymeric pharmaceutically acceptable excipient is a cellulose derivative, a saccharide or polysaccharide, a polyhydric alcohol, a poly(oxyethylene)-poly(oxypropylene) block copolymer, a vinyl derivative or polymer or copolymer thereof, or a acrylic acid derivative, or a combination thereof.

7. The formulation of claim 6 wherein said cellulose derivative is ethyl cellulose, methylcellulose, hydroxypropylmethylcellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxymethyl cellulose, hydroxypropyl ethylcellulose, carboxy ethylcellulose, carboxymethyl ethylcellulose, carboxymethyl hydroxyethylcellulose, hydroxyethylmethyl carboxymethyl cellulose, hydroxyethyl methyl cellulose, carboxymethyl cellulose, methylhydroxyethyl cellulose, methylhydroxypropyl cellulose, carboxymethyl sulfoethyl cellulose, sodium carboxy methyl cellulose, cellulose acetate, cellulose acetate phthalate, cellulose acetate butyrate, hydroxypropylmethylcellulose acetate succinate, hydroxypropylmethylcellulose phthalate, hydroxymethyl ethylcellulose phthalate, cellulose acetate phthalate, cellulose acetate succinate, cellulose acetate maleate, cellulose acetate trimelliate, cellulose benzoate phthalate, cellulose propionate phthalate, methylcellulose phthalate, or ethylhydroxy ethylcellulose phthalate, or a combination thereof.

8. The formulation of claim 6 wherein said vinyl derivative or polymer or copolymer thereof is polyvinylacetate aqueous dispersion (Kollicoat®

SR 30D), copolymers of vinyl pyrrolidone, polyvinyl alcohol phthalate, polyvinylacetal phthalate, polyvinyl butylate phthalate, polyvinylacetoacetal phthalate, or polyvinylpyrrolidone, or a combination thereof.

9. The formulation of claim 6 wherein said acrylic acid derivative is methacrylic acid, polymethacrylic acid, polyacrylate, or polymethacrylate, or a combination thereof, said polyacrylate being a) copolymer formed from monomers selected from the group consisting of methacrylic acid, methacrylic acid esters, acrylic acid and acrylic acid esters;

b) copolymer formed from monomers selected from the group consisting of butyl methacrylate, (2-dimethylaminoethyl)methacrylate and methyl methacrylate;

c) copolymer formed from monomers selected from the group consisting of ethyl acrylate, methyl methacrylate and trimethylammonioethyl methacrylate chloride;

or d) copolymer of acrylate and methacrylates with/without quarternary ammonium group in combination with sodium carboxymethylcellulose.

10. The formulation of claim 5 wherein said non-polymeric pharmaceutically acceptable excipient is spermaceti wax, carnauba wax, Japan wax, bayberry wax, flax wax, beeswax, yellow wax, Chinese wax, shellac wax, lanolin wax, sugarcane wax, candelilla wax, castor wax, paraffin wax, microcrystalline wax, petrolatum wax, carbowax, mineral waxes, glyceryl monostearate, glyceryl distearate, glyceryl tristearate, glyceryl dipalmitate, glyceryl tripalmitate, glyceryl monopalmitate, glyceryl palmitostearate, glyceryl dilaurate, glyceryl trilaurate, glyceryl monolaurate, glyceryl didocosanoate, glyceryl tridocosanoate, glyceryl monodocosanoate, glyceryl monocaproate, glyceryl dicaproate, glyceryl tricaproate, glyceryl monomyristate, glyceryl dimyristate, glyceryl trimyristate, glyceryl monodecenoate, glyceryl didecenoate, glyceryl tridecenoate, glyceryl behenate, polyglyceryl diisostearate, lauroyl macrogolglycerides, oleoyl macrogolglycerides, stearoyl macrogolglycerides, hydrogenated palm kernel oil, hydrogenated peanut oil, hydrogenated palm oil, hydrogenated rapeseed oil, hydrogenated rice bran oil, hydrogenated soybean oil, hydrogenated sunflower oil, hydrogenated castor oil, hydrogenated cottonseed oil, decenoic acid, docosanoic acid, stearic acid, palmitic acid, lauric acid, myristic acid, cetyl alcohol, or stearyl alcohol, or a combination thereof.

12. The formulation of claim 5 wherein said carbomer is carbomer 934, carbomer 971, or carbomer 974, or a combination thereof.

13. The formulation of claim 5 wherein said ion exchange resin is a cationic ion exchange resin.

14. The formulation of claim 5 wherein said cyclodextrin is α

-cyclodextrin, β

-cyclodextrin, γ

-cyclodextrin, dimethyl-β

-cyclodextrin, trimethyl-β

-cyclodextrin, hydroxymethyl-β

-cyclodextrin, hydroxypropyl-β

-cyclodextrin, hydroxyethyl-β

-cyclodextrin, β

-cyclodextrin sulfate, β

-cyclodextrin sulfonate, or β

-cyclodextrin sulfobutyl ether, dihydroxypropyl-β

-cyclodextrin, glucosyl-α

-cyclodextrin, glucosyl-β

-cyclodextrin, diglucosyl-β

-cyclodextrin, maltosyl-γ

-cyclodextrin, maltosyl-γ

-cyclodextrin, maltosyl-γ

-cyclodextrin, maltotriosyl-β

cyclodextrin, maltotriosyl-γ

-cyclodextrin, dimaltosyl-β

-cyclodextrin, maltosyl-β

-cyclodextrin/dimaltosyl-β

-cyclodextrin, or a combination thereof.

16. The formulation of claim 5 wherein said taste-masking agent is in the range of about 1% to about 95% by weight of the formulation.

17. The formulation of claim 5 wherein said taste-masking agent is in the range of about 2% to about 75% by weight of the formulation.

18. The formulation of claim 5 wherein said taste-masking agent is in the range of about 5% to about 60% by weight of the formulation.

19. The formulation of claim 1 wherein said influenza antiviral is taste-masked by physical mixing, coating, complexation, adsorption or salt formation using said taste-masking agent.

20. The formulation of claim 1 wherein said excipient is a binder, disintegrant, superdisintegrant, diluent, salivating agent, surfactant, flavor, sweetener, colorant, souring agent, viscolizer, glidant, lubricant, solubilizer, or stabilizer.

21. The formulation of claim 1 wherein said influenza antiviral is in the form of powder, granules, pellets, beads, minitablets, or a combination thereof

22. The formulation of claim 1 wherein said formulation is in the form of a dispersible tablet, orally disintegrating tablet, effervescent tablet, chewable tablet, sprinkle granules, dry suspension or dry syrup for reconstitution, quick melt wafers, lozenge, or chewing gum.

23. The formulation of claim 1 further comprising an additional active agent, said active agent being nelfinavir, abacavir, acemetacin, acetoniode, acetyl salicylic acid, aciclovir, acrivastine, acyclovir, adefovir, alclofenac, alminoprofen, amastatin, amprenavir, antipain, aprotinin, arbidol, astemizole, atazanavir, atorvastatin, atripla, azapropazone, azelastine, benorylate, benoxaprofen, betastatin, boceprevir, bucloxic acid, budesonide, caffeine, carprofen, celecoxib, cerivastatin, cetirizine, choline magnesium trisalicylate, cidofovir, clidanac, clopinac, combivir, darunavir, delavirdine, deracoxib, desloratadine, diclofenac, didanosine, diflunisal, docosanol, droxicam, ebastine, edoxudine, efavirenz, elastatinal, emtricitabine, enfuvirtide, entecavir, epinastine, etodolac, etoricoxib, famciclovir, fenbufen, fenclofenec, fenoprofen, fentiazac, feprazone, fexofenadine, floctafenine, flufenamic acid, flufenisal, fluprofen, flurbiprofen, fluticosone propionate, fluvastatin, fomivirsen, fosamprenavir, foscarnet, fosfonet, furofenac, ganciclovir, ibacitabine, ibufenac, ibuprofen, idoxuridine, imiquimod, imunovir, indinavir, indomethacin, indoprofen, isoxepac, isoxicam, ketoprofen, ketorolac, lamivudine, leupeptin, licofelone, lopinavir, lortadine, lovastatin, loviride, lumiracoxib, maraviroc, meclofenamic acid, mefenamic acid, miroprofen, mizolastine, mometasone furoate mononhydrate, moroxydine, nabumetone, naproxen, nelfinavir, nevirapine, nexavir, niflumic acid, norastemizole, oxaprozin, oxipinac, oxyphenbutazone, parecoxib, penciclovir, pepstatin, peramivir, phenylbutazone, piprofen, piroxicam, pirprofen, pleconaril, prapoprofen, pravastatin, proglumetacin, prometazine, raltegravir, ribavirin, ritonavir, rofecoxib, saquinavir, simvastatin, stavudine, sudoxicam, sulindac, suprofen, tenofovir, tenoxicam, terfenadine, tepoxalin, thiophosphonoformic acid, tiaprofenic acid, tiopinac, tioxaprofen, tipranavir, tolfenamic acid, tolmetin, triamcinalone, trifluridine, trizivir, tromantadine, truvada, valaciclovir, valdecoxib, valganciclovir, vicriviroc, vidarabine, viramidine, zalcitabine, zidometacin, zidovudine, zomepirac, ceftriaxone, cefotaxime, vancomycin, meropenem, cefepime, ceftazidime, cefuroxime, nalcillin, oxacillin, ampicillin, ticarcillin, ticarcillin/clavulinic acid, ampicillin/sulbactam, trimethoprim-sulfamethoxazole, clindamycin, synercid, amoxicillin, amoxicillin/clavulinic acid, cefuroxime, trimethoprim/ sulfamethoxazole, azithromycin, dicloxacillin, ciprofloxacin, levofloxacin, cefixime, cetpodoxime, loracarbef, cefadroxil, cefabutin, cefdinir or cephradine.

3. (canceled)

11. (canceled)

15. (canceled)

24. (canceled)