Hydrophilic polystyrene graft copolymer vehicle for intravaginal administration of pharmacologically active agents

• US 5,814,329 A
• Filed: 11/12/1996
• Issued: 09/29/1998
• 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:
  US08/746,327
• Time in Patent Office: 686 Days
• Field of Search: 424/772.1, 424/430, 424/433, 514/967
• US Class Current: 424/433
• 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

Abstract

This invention pertains to the vaginal delivery of pharmacologically active agents and to polymeric formulations that allow for a prolonged release of the active agents in the vaginal environment. More specically the invention pertains to compositions for the delivery of drugs intravaginally 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 hydrophilic monomer having an ethylenically unsaturated functional group.

Claims

1. A sustained release vaginal dosage form 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 dosage form in an amount sufficient to cause said dosage form to form a water swollen but insoluble jelly like mass upon contact with the biological environment.

2. A sustained release vaginal dosage form as in claim 1 where the weight percent of the drug to be delivered is between 0.001 and 40.

3. A sustained release vaginal dosage form as in claim 1 where the hydrophilic monomer further comprises a neutral monomer.

4. A sustained release vaginal dosage form as in claim 1 where the hydrophilic monomer is acrylic acid.

5. A sustained release vaginal dosage form as in claim 3 where the hydrophilic neutral monomer is N,N-dimethylacrylamide.

6. A sustained release vaginal dosage form as in claim 1 in the form of powder.

7. A dispersion comprising a sustained release vaginal dosage form as in claim 1, and any acceptable liquid pharmaceutical excipient.

8. A sustained release vaginal dosage form as in claim 1 as a unit dose insert.

9. A sustained release vaginal dosage form as in claim 1 where the drug is a spermicide.

10. A sustained release vaginal dosage form as in claim 9 where the spermicidal drug is Nonoxynol 9.

11. A sustained release vaginal dosage form as in claim 1 where the drug is a progestin.

12. A sustained release vaginal dosage form as in claim 11 where the drug is progesterol.

13. A sustained release vaginal dosage form as in claim 1 where the drug is an estrogen.

14. A sustained release vaginal dosage form as in claim 13 where the drug is estradiol.

15. A sustained release vaginal dosage form as in claim 13 where the drug is estriol.

16. A sustained release vaginal dosage form as in claim 1 where the drug is an antifungal agent.

17. A sustained release vaginal dosage form as in claim 16 where the drug is miconazole nitrate.

18. A sustained release vaginal dosage form as in claim 16 where the drug is clotrimazole.

19. A sustained release vaginal dosage form as in claim 1 where the drug is a protein.

20. A sustained release vaginal dosage form as in claim 1 where the drug is a peptide.

21. A sustained release vaginal dosage form as in claim 1 where the drug is systemically absorbed and has therapeutic effectiveness in parts of the body other than the vagina.

27. A composition comprising the sustained release vaginal dosage form as in claim 1 and at least one compatible hydrophilic polymer.

22. A sustained release vaginal dosage form 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%,

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

28. A composition comprising the sustained release vaginal dosage form as in claim 22 plus a compatible hydrophilic polymer.

23. A sustained release vaginal dosage form 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 dosage form in an amount sufficient to cause said dosage form to form a water swollen but insoluble jelly like mass upon contact with the biological envronment.

24. A sustained release vaginal dosage form as in claim 23 where the plasticizer is polyethylene glycol.

29. A composition comprising the sustained release vaginal dosage form as in claim 23 plus a compatible hydrophilic polymer.

25. A sustained release vaginal dosage form 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%, and

( C) a plasticizer

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

26. A sustained release vaginal dosage form as in claim 25 where the plasticizer is polyethylene glycol.

30. A composition comprising the sustained release vaginal dosage form as in claim 25 and at least one compatible hydrophilic polymer.

31. A sustained release vaginal dosage form 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%,

(C) an adjuvant selected from the group consisting of;

(1) a plasticizer, or

(2) a water soluble or water swellable compatible polymer;

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

32. A sustained release vaginal dosage form 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%, and

(C) an adjuvant selected from the group consisting of;

(1) a plasticizer, or

(2) a water soluble or water swellable compatible polymer.

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