Film-forming powder, compositions containing it, methods for their preparation and their uses

• US 20030096012A1
• Filed: 03/14/2002
• Published: 05/22/2003
• 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:
  US10/097,781
• Publication Number:
  US 20030096012A1
• Time in Patent Office: Days
• US Class Current: 424/489
• 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 film-forming powder comprising at least one active substance, at least one bioadhesive agent, and optionally surfactants, wetting agents, plasticizers, binders, retardants, penetration promoters and bioerodible diluents.

Claims

1. Film-forming powder comprising at least one active substance, at least one bioadhesive agent, and optionally surfactants, wetting agents, plasticizers, binders, retardants, penetration antrancers and bioerodible diluents.

2. Film-forming powder according to claim 1, wherein the active substance is micronized.

3. Film-forming powder according to either of claim 1, wherein the powder is micronized.

4. Film-forming powder according to claim 1, wherein the active substance is 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, esomeprazole, melagatran (in case of thrombosis), rosuvastatin, ezetimide, pitavastatin (hyperlipidaemia), mitiglinide (type II diabetes), cilomilast, viozan (asthma), aripipazole (psychiatry), omapatrilat (hypertensive), orzel (cancerology), caspofungin acetate, voriconazole (infections), novel COX inhibitors such as etoricoxib (inflammation), valdecoxib (arthritis) and parecoxib, substance P antagonist (depression), darifenacin (urology), eletriptan (migraine), alosetron, tegaserod, capravirine (HIV) and combinations thereof.

5. Film-forming powder according to any one of claims 1 to 4, characterized in that the bioadhesive agent is selected from the group consisting of methyl cellulose, carboxymethyl cellulose, carboxymethyl cellulose sodium, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose sodium, polyvinylpyrrolidone, polyvinyl alcohols, polyisobutylene, polyisopropene, xanthan gum, locust bean gum, chitosan, chitosan chloride, polycarboxylates, carbomers such as carbopol, 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, starches, dextran and mixtures thereof.

6. Film-forming powder according to claim 1, wherein the surfactant is preferably selected from nonionic surfactants such as polyoxyethylene sorbitan (fatty acid ester), polyoxyethylene alkyl ether, polyoxyethylene derived from castor oil, and mixtures thereof.

7. Film-forming powder according to claim 1, wherein the wetting agent is selected from the group consisting of polyols such as sorbitol, glycerin, polyethylene glycol and mixtures thereof.

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

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

10. Film-forming powder according to claim 1, wherein the retardant is selected from the group consisting of hydroxypropyl methyl cellulose acetate or succinate, hydroxypropyl methyl cellulose, hydroxypropyl cellulose, ethyl cellulose, hydroxyethyl cellulose, carboxymethyl cellulose sodium, polyvinyl alcohols, hydrocolloids such as:

pectins, alginates, guar gum, xanthan gum, gum Arabic, agar, dextrin, carragheenan, polyethylene oxide, carbomers, polymers and copolymers of acrylic acid, of methyl methacrylate, of polyvinyl acetate, of carboxymethyl acetate and mixtures thereof.

11. Film-forming powder according to claim 1, wherein the bioerodible diluent is selected from the group consisting of calcium or sodium carbonate or bicarbonate, sucrose, mannitol, xylitol, sorbitol, lactose, cellulose or microcrystalline cellulose powder, starch and its derivatives, dibasic calcium phosphate, tribasic calcium phosphate, calcium sulphate, dextrates, dextrins, dextrose excipients, fructose, kaolin, lactitol and mixtures thereof.

12. Film-forming powder according to claim 1, wherein the penetration entrancer is selected from the group consisting of aliphatic fatty acid esters such as isopropyl myristate, fatty acids such as oleic acid;

alcohols or polyols such as ethanol, propylene glycol and polyethylene glycol;

components of essential oils and terpenic derivatives (such as eugenol, geraniol, nerol, eucalyptol, menthol);

surfactants;

moisturizers such as glycerin, urea;

keratolytics such as alpha-hydroxy acids and mixtures thereof.

13. Film-forming powder according to claim 1, having a particle size of between 0.01 μ

m and 1000 μ

m, preferably between 0.1 μ

m and 100 μ

m and more preferably still between 1 μ

m and 50 μ

m.

14. Pharmaceutical, cosmetic or nutraceutical composition comprising a powder forming a film after application in situ according to any one of claim 1.

15. Composition according to claim 14, administered by the mucosal route.

16. Composition according to claim 15, administered through the buccal mucosa, the nasal mucosa or the vaginal mucosa.

17. Composition according to claim 14, administered by the transdermal route with local or systemic effect

18. Composition according to claim 14, being in pulverizable form.