Mucoadhesive compositions for administration of biologically active agents to animal tissue

• US 5,942,243 A
• Filed: 05/12/1998
• Issued: 08/24/1999
• Est. Priority Date: 11/12/1996
• Status: Expired due to Term

• Current Assignee: Polytherapeutics, Inc.
• Original Assignee: Polytherapeutics, Inc.
• Inventors: Shah, Kishore R.
• Primary Examiner(s): Kulkosky, Peter F.
• Application Number:
  US09/076,216
• Time in Patent Office: 469 Days
• Field of Search: 424/435, 424/434
• US Class Current: 424/434
• 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 9/0034 Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
• CPC Class Codes: A61K 9/0036 Devices retained in the vagina or cervix for a prolonged period, e.g. intravaginal rings, medicated tampons, medicated diaphragms
• CPC Class Codes: A61K 9/006 Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
• CPC Class Codes: A61K 9/06 Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels composition of ointments, creams or gels A61K47/00
• CPC Class Codes: A61K 9/7007 Drug-containing films, membranes or sheets A61K9/0041, A61K9/0043, A61K9/006, A61K9/0063 take precedence
• CPC Class Codes: A61P 15/16 Masculine contraceptives
• CPC Class Codes: A61P 31/10 Antimycotics

Abstract

This invention pertains to mucoadhesive compositions for the delivery of pharmacologically active agents, and to polymeric formulations that allow for a prolonged, sustained release of the active agents. More specically the invention pertains to compositions for the delivery of drugs to mucosal tissue, said composition comprising a drug or a plurality of drugs to be delivered and a thermoplastic graft copolymer, said graft copolymer being the reaction product of a polystyrene macromonomer having an ethylenically unsaturated functional group, and at least one acidic hydrophilic monomer having an ethylenically unsaturated functional group.

Claims

1. A mucoadhesive hydrophilic drug delivery system comprising:

(A) a drug or a plurality of drugs to be delivered, and

(B) a drug delivery vehicle consisting essentially of a thermoplastic graft copolymer, said graft copolymer being a reaction product of;

(1) a polystyrene macromonomer having an ethylenically unsaturated functional group, and

(2) at least one hydrophilic acidic monomer having an ethylenically unsaturated functional group,

wherein the weight percent of the polystyrene macromonomer in the graft copolymer is between about 1 and about 20%, and the weight percent of the total hydrophilic monomer in the graft copolymer is between 80 and 99%, wherein at least about 10% of said total hydrophilic monomer is acidic, said graft copolymer when fully hydrated having an equilibrium water content of at least 90%,

said graft copolymer being present in said drug delivery system in an amount sufficient to cause said drug delivery system to form a water swollen but insoluble jelly like mass upon contact with the biological environment.

3. A mucoadhesive hydrophilic drug delivery system as in claim 1 wherein the weight percent of the drug to be delivered is between 0.001 and 40.

4. A mucoadhesive hydrophilic drug delivery system as in claim 1 wherein the hydrophilic monomer further comprises a neutral monomer.

5. A mucoadhesive hydrophilic drug delivery system as in claim 1 wherein the hydrophilic monomer is acrylic acid.

6. A mucoadhesive hydrophilic drug delivery system as in claim 4 wherein the hydrophilic neutral monomer is N,N-dimethylacrylamide.

7. A mucoadhesive hydrophilic drug delivery system as in claim 1 in the form of powder.

8. A dispersion comprising a mucoadhesive hydrophilic drug delivery system as in claim 1, and any acceptable liquid pharmaceutical excipient.

9. A sustained release mucoadhesive hydrophilic drug delivery system as in claim 1 packaged in a unit dose.

10. A mucoadhesive hydrophilic drug delivery system as in claim 1 wherein the drug is a spermicide.

11. A mucoadhesive hydrophilic drug delivery system as in claim 1 wherein the spermicidal drug is Nonoxynol 9.

12. A mucoadhesive hydrophilic drug delivery system as in claim 1 wherein the drug is selected from the group consisting of:

progesterone, estrogen, estradiol, and estriol.

13. A mucoadhesive hydrophilic drug delivery system as in claim 1 wherein the drug is an antifungal agent.

14. A mucoadhesive hydrophilic drug delivery system as in claim 13 wherein the drug is selected from the group consisting of:

miconazole nitrate and clotrimazole.

15. A mucoadhesive hydrophilic drug delivery system as in claim 1 wherein the drug is a protein.

16. A mucoadhesive hydrophilic drug delivery system as in claim 1 wherein the drug is a peptide.

17. A mucoadhesive hydrophilic drug delivery system as in claim 1 wherein the drug is systemically absorbed and has therapeutic effectiveness in a distal part of the body.

21. The mucosal drug delivery system as in claim 1, wherein the dosage form is a viscous solution.

2. A sustained release mucoadhesive hydrophilic drug delivery system comprising:

(A) a drug or a plurality of drugs to be delivered, and

(B) a drug delivery vehicle consisting essentially of a thermoplastic graft copolymer, said graft copolymer being a reaction product of;

(1) a polystyrene macromonomer having an ethylenically unsaturated functional group, and

(2) at least one hydrophilic acidic monomer having an ethylenically unsaturated functional group,

wherein the weight percent of the polystyrene macromonomer in the graft copolymer is between about 1 and about 20%, and the weight percent of the total hydrophilic monomer in the graft copolymer is between 80 and 99%, wherein at least about 10% of said total hydrophilic monomer is acidic, said graft copolymer when fully hydrated having an equilibrium water content of at least 90%,

said graft copolymer being present in said drug delivery system in an amount sufficient to cause said drug delivery system to form a water swollen but insoluble jelly like mass upon contact with the biological environment.

18. A sustained release mucoadhesive hydrophilic drug delivery system comprising:

(A) a drug or a plurality of drugs to be delivered, and

(B) a drug delivery vehicle consisting essentially of a thermoplastic graft copolymer, said graft copolymer being a reaction product of;

(1) a polystyrene macromonomer having an ethylenically unsaturated functional group, and

(2) at least one hydrophilic acidic monomer having an ethylenically unsaturated functional group,

(3) and a hydrophilic neutral monomer having an ethylenically unsaturated functional group,

wherein the weight percent of the polystyrene macromonomer in the graft copolymer is between about 1 and about 20%, and the weight percent of the total hydrophilic monomer in the graft copolymer is between 80 and 99%, wherein at least about 10% of said total hydrophilic monomer is acidic, said graft copolymer when fully hydrated having an equilibrium water content of at least 90%,

(C) a plasticizer

said graft copolymer being present in said drug delivery system in an amount sufficient to cause said drug delivery system to form a water swollen but insoluble jelly like mass upon contact with the biological environment.

19. A sustained release mucoadhesive hydrophilic drug delivery system as in claim 18 wherein the plasticizer is polyethylene glycol.

20. A composition comprising the sustained release mucoadhesive hydrophilic drug delivery system as in claim 18 further comprising at least one compatible hydrophilic polymer.