Micronized film-forming powder comprising an active substance

• US 20050042173A1
• Filed: 11/21/2002
• Published: 02/24/2005
• Est. Priority Date: 11/21/2001
• Status: Abandoned Application

• Current Assignee: Besins International Belgique, Galenix Innovations
• Original Assignee: Besins International Belgique, Galenix Innovations
• Inventors: Cornu, Philippe, Besse, Jerome, Besse, Laurence, Taravella, Brigitte
• Application Number:
  US10/496,094
• Publication Number:
  US 20050042173A1
• Time in Patent Office: Days
• US Class Current: 424/46
• CPC Class Codes: A61K 9/006 Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
• CPC Class Codes: A61K 9/7015 Drug-containing film-forming compositions, e.g. spray-on
• CPC Class Codes: A61P 11/08 Bronchodilators
• CPC Class Codes: A61P 15/16 Masculine contraceptives
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 5/30 Oestrogens
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Abstract

The present invention relates to a micronized film-forming powder having a particle size of at most 100 μm and comprising a combination of at least one active substance, at least one bioadhesive agent, and at least a plasticizer.

Claims

1. Micronized film-forming powder having a particle size of at most 100 μ

m and comprising the combination of at least an active substance, at least a biocompatible adhesive agent and at least a plasticizer.

2. Micronized film-forming powder according to claim 1, characterized in that the active substance is micronized.

3. Micronized film-forming powder according to claim 1, characterized in that it has a particle size of at most 50 μ

m.

4. Micronized film-forming powder according to claim 1, which has a particle size of at most 20 μ

m.

5. Micronized film-forming powder according to claim 1, which further comprises at least one compound selected from the group consisting of a surfactant, a wetting agent, a binder, a retardant, a penetration enhancer, a bioerodible diluent, a colorant, a flavor, a pH controlling agent and a combination of at least two of these compounds.

6. Micronized film-forming powder according to claim 1, wherein the active substance is a member selected from the group consisting of estradiol and its derivatives, norethisterone acetate, progesterone, testosterone, trinitrine, fentanyl, nitroglycerine, nicotine (S(−

)-nicotine), scopolamine, clonidine, isosorbide dinitrate, levonorgestrel in combination with ethinylestradiol or with estradiol, androstanolone, alclometasone dipropionate, acetazolamide, acyclovir, adapalene, alclomethasone dipropionate, amcinonide, ameleine, bamethan sulphate+escin, betamethasone valerate, betamethasone dipropionate, bufexamac, caffeine, calcipotriol monohydrate, cetrimonium bromide, clobetasol propionate, crilanomer, desonide, dexpanthenol, diclofenac, diflucortolone, valerate, difluprednate, diphenydramine hydrochloride, econazole nitrate, erythromycin, flumetasone pivalate, fluocinolone acetonide, fluocinodine, fluocortolone, fluocortolone hexanoate, fluocortolone pivalate, hydrocortisone, hydrocortisone acetate, ibacitabin, ibuprofen, imiquimod, ketoconazole, ketoprofen, lidocaine, metronidazole, miconazole nitrate, minoxidil, niflumide acid, penciclovir, benzoyl peroxide, piroxam, iodinated povidone, promestriene, pyrazonibutasone, roxithromycin, sulphacetamide, triamconolone, tazarotene, tretinoin and isotretinoin, triclocarban, vidarabine monophosphate, β

₃-adrenergic agonist, growth hormone, oxybutinin, buprenorphine, pergolide, estradiol+nestorone, nesterone, 7α

-methyl-19-nortesterone, mecamylamine (antagonist of nicotine)+nicotine, salbutamol, selegiline, buspirone, ketotifen, lidocaine, testosterone+estradiol, ketorolac, eptazocine, insulin, α

-interferon, prostaglandines, 17β

-estradiol+norethindrone acetate, 5-aminolevulinic acid, benzodiazepine alprozolam, diclofenac, fenoprofen, flubiprofen, ketoprofen, methyl phenidate, miconazole, piroxicam, bruprenorphine, alprozolam, dexmedetomidine, prazosin (α

-adrenergic antagonist), gestodene+ethinylestradiol, alprostadil, tulobuterol (β

-adrenergic agonist), ethinylestradiol+norelgestromin, ketorolac, physostigmine, lidocaine, medindolol (α

-adrenergic agonist), rotigotine (D2 dopamine antagonist), ethinylestradiol+norethindrone acetate, thiatolserine, and a combination of at least two thereof.

7. Micronized film-forming powder according to claim 1, wherein the active substance is a member selected from the group consisting of an emollient, a moisturizing agents, a vitamins, complex of fruit and an amino acid, and an antioxidant agents.

8. Micronized film-forming powder according to claim 1, wherein the active substance is a member selected from the group consisting of a vitamins, an inorganic salt, and brewer'"'"'s yeast.

9. Micronized film-forming powder according to claim 1, wherein the bioadhesive agent is a member selected from the group consisting of ethyl cellulose, methyl cellulose, carboxymethyl cellulose, carboxymethyl cellulose sodium, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose sodium, polyvinylpyrrolidone, a polyvinyl alcohol, polyisobutylene, polyisopropene, xanthan gum, locust bean gum, chitosan, chitosan chloride, a polycarboxylat, a carbomers acrylic/methacrylic acid copolymer, acrylic acid/acrylamide copolymer, acrylic acid/methyl methacrylate copolymer, acrylic acid/polyethylene glycol copolymer, polyacrylic acid/butyl acrylate copolymer, HEMA (2-hydroxyethyl methacrylate) copolymerized with Polymeg®

(polytetramethylene glycol), Cydot®

marketed by 3M (carbopol combined with polyisobutylene), pectin (of low viscosity), polyethylene oxide, methyl vinyl ether/maleic anhydride copolymer, tragacanth, monomethyl ether, monomethacrylate, drum dried waxy maize starch, sodium stearyl fumarate, sodium hyaluronate, guar gum, sodium alginate, a starches, dextran and a mixture&

thereof.

10. Micronized film-forming powder according to claim 1, wherein the plasticizer is a member selected from the group consisting of dibutyl phthalate, dibutyl sebacate, acetyltributyl citrate, acetyltriethyl citrate, tributyl citrate, tributylethyl citrate, triacetin, PEG, propylene glycol, glycerol, a glycerol monoester and a derivatives thereof, castor oil and a mixtures thereof.

11. Micronized film-forming powder according to claim 1, wherein the surfactant is at least one nonionic surfactants.

12. Micronized film-forming powder according to claim 1, wherein the wetting agent comprises at least one polyol.

13. Micronized film-forming powder according to claim 1, wherein the binder is a member selected from the group consisting of acacia, alginic acid, carboxymethyl cellulose sodium, microcrystalline cellulose, a dextrin, ethyl cellulose, gelatin, glucose, guar gum, hydroxypropyl methyl cellulose, methyl cellulose, polyethylene oxide, povidone, pregelatinized starch and a mixtures thereof.

14. Micronized film-forming powder according to claim 1, wherein the retardant is a member selected from the group consisting of hydroxypropyl methyl cellulose acetate or succinate, hydroxypropyl methyl cellulose, hydroxypropyl cellulose, ethyl cellulose, hydroxyethyl cellulose, carboxymethyl cellulose sodium, a polyvinyl alcohol, a hydrocolloid an alginate, guar gum, xanthan gum, gum Arabic, agar, dextrin, carragheenan, polyethylene oxide, a carbomer, a polymer and or copolymer of acrylic acid, of methyl methacrylate, of polyvinyl acetate, or of carboxymethyl acetate, and a mixtures thereof.

15. Micronized film-forming powder according to claim 1, wherein the bioerodible diluent is a member selected from the group consisting of calcium or sodium carbonate or bicarbonate, sucrose, mannitol, xylitol, sorbitol, lactose, cellulose or microcrystalline cellulose powder, starch or a derivatives thereof, dibasic calcium phosphate, tribasic calcium phosphate, calcium sulphate, a dextrat, a dextrin, a dextrose excipient, fructose, kaolin, lactitol and a mixtures thereof.

16. Micronized film-forming powder according to claim 1, wherein the penetration enhancer is a member selected from the group consisting of an aliphatic fatty acid esters a fatty acid, an alcohol or polyol, an alpha-hydroxy acids and a mixture thereof.

17. Pharmaceutical, cosmetic or nutraceutical composition comprising a micronized film-forming powder according to claim 1 forming a film after application in situ on a hydrated support.

18. A method which comprises administering a composition according to claim 17, by the mucosal route.

19. A method which comprises administering a composition according to claim 17, on buccal mucosa, nasal mucosa or vaginal mucosa.

20. A method which comprises administering a composition according to claim 17, by the transdermal route with local or systemic effect.

21. Composition according to claim 17, characterized in that it is in pulverizable form.

22. Micronized film-forming powder according to claim 9 wherein the carbomer is carbopol.

23. Micronized film-forming powder according to claim 11 wherein the nonionic surfactant comprises at least one member selected from the group consisting of polyoxyethylene sorbitan (fatty acid ester), polyoxyethylene alkyl ether, and polyoxyethylene derived from castor oil.

24. Micronized film-forming powder according to claim 12 wherein the polyol comprises at least one member selected from the group consisting of sorbitol, glycerin, and polyethyleneglycol.

25. Micronized film-forming powder according to claim 14 wherein the hydrocolloid is a pectin.

26. Micronized film-forming powder according to claim 16 wherein the aliphatic fatty acid ester is isopropyl myristate;

the fatty acid is oleic acid; and

the alcohol or polyol is ethanol, propylene glycol or polyethylene glycol.