Bioerodable film for delivery of pharmaceutical compounds of mucosal surfaces

• US 6,159,498 A
• Filed: 09/01/1998
• Issued: 12/12/2000
• Est. Priority Date: 10/18/1996
• Status: Expired due to Term

• Current Assignee: Arius Two Incorporated (Biodelivery Sciences International Incorporated)
• Original Assignee: Virotex Corporation (TOLMAR Holding, Inc.)
• Inventors: Osborne, David W., Tapolsky, Gilles H.
• Primary Examiner(s): Webman, Edward J.
• Application Number:
  US09/144,827
• Time in Patent Office: 833 Days
• Field of Search: 424/449, 424/448, 424/434
• US Class Current: 424/449
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/245 Amino benzoic acid types, e.g. procaine, novocaine salicylic acid esters A61K31/60
• CPC Class Codes: A61K 31/4178 not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
• CPC Class Codes: A61K 31/4515 having a butyrophenone group in position 1, e.g. haloperidol pipamperone A61K31/4545
• CPC Class Codes: A61K 31/568 substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 47/38 Cellulose; Derivatives thereof
• CPC Class Codes: A61K 9/006 Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
• CPC Class Codes: A61K 9/7023 Transdermal patches and similar drug-containing composite devices, e.g. cataplasms galenical aspects of iontophoretic devices A61K9/0009; microneedle arrays A61K9/0021; buccal patches A61K9/006
• CPC Class Codes: A61K 9/7069 obtained otherwise than by reactions only involving carbon to carbon unsaturated bonds, e.g. polysiloxane, polyesters, polyurethane, polyethylene oxide
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

The present invention relates to water-soluble, bioerodable pharmaceutical delivery device for application to mucosal surfaces. The device comprises an adhesive layer and a non-adhesive backing layer, and the pharmaceutical may be provided in either or both layers. Upon application, the device adheres to the mucosal surface, providing drug delivery and protection to the treatment site.

Claims

1. A biodegradable, water-soluble pharmaceutical carrier device comprising a layered flexible film having a first water-soluble adhesive layer to be placed in contact with the mucosal surface and a second, water-soluble non-adhesive backing layer, and a pharmaceutical or combination of pharmaceuticals incorporated with said first or second layer, wherein said first water-soluble adhesive layer comprises hydroxyethyl cellulose, polyacrylic acid, and sodium carboxymethyl cellulose;

and said second water-soluble non-adhesive backing layer comprises hydroxyethyl cellulose.

2. The pharmaceutical carrier device of claim 1, wherein said pharmaceutical or combination of pharmaceuticals comprises an anti-inflammatory analgesic agent.

3. The pharmaceutical carrier device of claim 2, wherein said anti-inflammatory analgesic agent is acetaminophen, methyl salicylate, monoglycol salicylate, aspirin, mefenamic acid, flufenamic acid, indomethacin, diclofenac, alclofenac, diclofenac sodium, ibuprofen, ketoprofen, naproxen, pranoprofen, fenoprofen, sulindac, fenclofenac, clidanac, flurbiprofen, fentiazac, bufexamac, piroxicam, phenylbutazone, oxyphenbutazone, clofezone, pentazocine, mepirizole, or tiaramide hydrochloride.

4. The pharmaceutical carrier device of claim 1, wherein said pharmaceutical or combination of pharmaceuticals comprises an steroidal anti-inflammatory agent.

5. The pharmaceutical carrier device of claim 4, wherein said steroidal anti-inflammatory agent is hydrocortisone, predonisolone, dexamethasone, triamcinolone acetonide, fluocinolone acetonide, hydrocortisone acetate, predonisolone acetate, methylpredonisolone, dexamethasone acetate, betamethasone, betamethasone valerate, flumetasone, fluorometholone, or beclomethasone diproprionate.

6. The pharmaceutical carrier device of claim 1, wherein said pharmaceutical or combination of pharmaceuticals comprises a local anesthetic other than dyclonine HCl.

7. The pharmaceutical carrier device of claim 6, wherein said local anesthetic is dibucaine hydrochloride, dibucaine, lidocaine hydrochloride, lidocaine, benzocaine, p-buthylaminobenzoic acid 2-(di-ethylamino) ethyl ester hydrochloride, procaine hydrochloride, tetracaine, tetracaine hydrochloride, chloroprocaine hydrochloride, oxyprocaine hydrochloride, mepivacaine, cocaine hydrochloride, dyclonine, or piperocaine hydrochloride.

8. The pharmaceutical carrier device of claim 1, wherein said pharmaceutical or combination of pharmaceuticals comprises an antihistamine.

9. The pharmaceutical carrier device of claim 8, wherein said antihistamine is diphenhydramine hydrochloride, diphenhydramine salicylate, diphenhydramine, chlorpheniramine hydrochloride, chlorpheniramine malcate isothipendyl hydrochloride, tripelennamine hydrochloride, promethazine hydrochloride, or methdilazine hydrochloride.

10. The pharmaceutical carrier device of claim 1, wherein said pharmaceutical or combination of pharmaceuticals comprises a bactericide.

11. The pharmaceutical carrier device of claim 10, wherein said bactericide is thimerosal, phenol, thymol, benzalkonium chloride, benzethonium chloride, chlorhexidine, povidone iodide, cetylpyridinium chloride, eugenol, or trimethylammonium bromide.

12. The pharmaceutical carrier device of claim 1, wherein said pharmaceutical or combination of pharmaceuticals comprises a vasoconstrictor.

13. The pharmaceutical carrier device of claim 12, wherein said vasoconstrictor is naphazoline nitrate, tetrahydrozoline hydrochloride, oxymetazoline hydrochloride, phenylephrine hydrochloride, or tramazoline hydrochloride.

14. The pharmaceutical carrier device of claim 1, wherein said pharmaceutical or combination of pharmaceuticals comprises a hemostatic agent.

15. The pharmaceutical carrier device of claim 14, wherein said hemostatic agent is thrombin, phytonadione, protamine sulfate, aminocaproic acid, tranexamic acid, carbazochrome, carbaxochrome sodium sulfanate, rutin, or hesperidin.

16. The pharmaceutical carrier device of claim 1, wherein said pharmaceutical or combination of pharmaceuticals comprises a chemotherapeutic agent.

17. The pharmaceutical carrier device of claim 16, wherein said chemotherapeutic agent is sulfamine, sulfathiazole, sulfadiazine, homosulfamine, sulfisoxazole, sulfisomidine, sulfamethizole, or nitrofurazone.

18. The pharmaceutical carrier device of claim 1, wherein said pharmaceutical or combination of pharmaceuticals comprises an antibiotic.

19. The pharmaceutical carrier device of claim 18, wherein said antibiotic is penicillin, meticillin, oxacillin, cefalotin, cefalordin, erythromcycin, lincomycin, tetracycline, chlortetracycline, oxytetracycline, metacycline, chloramphenicol, kanamycin, streptomycin, gentamicin, bacitracin, or cycloserine.

20. The pharmaceutical carrier device of claim 1, wherein said pharmaceutical or combination of pharmaceuticals comprises a keratolytic agent.

21. The pharmaceutical carrier device of claim 20, wherein said keratolytic agent is salicylic acid, podophyllum resin, podolifox, or cantharidin.

22. The pharmaceutical carrier device of claim 1, wherein said pharmaceutical or combination of pharmaceuticals comprises a cauterizing agent.

23. The pharmaceutical carrier device of claim 22, wherein said cauterizing agent is chloroacetic acid or silver nitrate.

24. The pharmaceutical carrier device of claim 1, wherein said pharmaceutical or combination of pharmaceuticals comprises an antiviral.

25. The pharmaceutical carrier device of claim 24, wherein said antiviral is a protease inhibitor, a thymadine kinase inhibitor, a sugar synthesis inhibitor, a glycoprotein synthesis inhibitor, a structural protein synthesis inhibitor, an attachment inhibitor, an adsorption inhibitor, a nucleoside analog, acyclovir, penciclovir, valacyclovir, or ganciclovir.

26. The pharmaceutical carrier device of claim 1, wherein the pharmaceutical comprises between about 0.001 percent and about 30 percent by weight of the pharmaceutical carrier device.

27. The pharmaceutical carrier device of claim 26, wherein the pharmaceutical comprises between about 0.005 percent and about 20 percent by weight of the pharmaceutical carrier device.