Bioactive composition

• US 5,455,286 A
• Filed: 08/02/1994
• Issued: 10/03/1995
• Est. Priority Date: 06/27/1991
• Status: Expired due to Fees

• Current Assignee: Arthur H. Goldberg, Gordon L. Amidon, Ramachandran Chandrasekharan
• Original Assignee: Arthur H. Goldberg, Gordon L. Amidon, Ramachandran Chandrasekharan
• Inventors: Chandrasekharan, Ramachandran, Goldberg, Arthur H., Amidon, Gordon L.
• Primary Examiner(s): Michl, Paul R.
• Assistant Examiner(s): DeWitt, LaVonda R.
• Application Number:
  US08/284,171
• Time in Patent Office: 427 Days
• Field of Search: 523/122, 514/944, 424/403, 424/405, 424/480, 424/407, 424/409, 424/418, 424/465, 424/474, 424/477, 424/478, 427/2, 427/4, 427/336, 427/340, 427/341
• US Class Current: 523/122
• CPC Class Codes: A01N 25/24 containing ingredients to enhance the sticking of the active ingredients
• 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 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/0043 Nose

Abstract

An improved bioactive agent delivery composition and method of application are described. The composition comprises a bioactive agent, a hydrophilic polymer in an incompletely hydrated state and a substantially water-miscible solvent system. The agent and polymer are essentially dissolved in the solvent system to form a sprayable composition having a viscosity of less than 350 cP. Upon dilution with water, the viscosity of the composition increases to in excess of 1000 cP to produce a retentive coating at the site of application which provides enhanced bioavailability of the agent.

Claims

1. A bioactive composition comprising:

a. bioactive agent;

b. hydrophilic polymer in an incompletely hydrated state; and

c. substantially water-miscible solvent system;

said system maintaining said agent and polymer in essentially dissolved form whereby said composition has a viscosity of less than 350 cP, which viscosity increases to in excess of 1000 cP upon dilution with water.

2. The bioactive agent delivery composition of claim 1 wherein the hydrophilic polymer is an ionic polymer.

3. The bioactive agent delivery composition of claim 1 wherein the hydrophilic polymer is a neutral polymer.

4. The composition of claim 1 wherein the hydrophilic polymer is a salt of an acidic ionic polymer and a neutralizing agent selected from the group consisting of inorganic bases and organic amines.

5. The composition of claim 4 wherein the neutralizing agent is an organic amine and is selected from the group consisting of triethanolamine, diisopropanolamine, monoethanolamine, basic amino acids and amine surfactants.

6. The composition of claim 1 wherein the hydrophilic polymer is a salt of a basic polymer and an inorganic acid neutralizing agent.

7. The composition of claim 1 wherein the solvent system comprises polypropylene glycol.

8. The composition of claim 1 wherein the solvent system comprises non-aqueous, pharmaceutically approved, parenteral vehicle.

9. The composition of claim 8 wherein the non-aqueous, pharmaceutically approved, parenteral vehicle is selected from the group consisting of dimethylacetamide, ethyl lactate, ethyl carbonate, dimethylformamide, dimethyl sulfoxide, and dioxolanes.

10. The composition of claim 1 wherein the solvent system comprises an organic solvent and an oil solvent.

11. The composition of claim 10 wherein the oil solvent is a hydrophobic organic substance.

12. The composition of claim 10 wherein the oil solvent is selected from the group consisting of fixed oils, and essential oils.

13. The composition of claim 1 which additionally comprises an emulsifying agent.

14. The composition of claim 13 wherein the emulsifying agent comprises a non-ionic surfactant of HLB less than about 15.

15. The composition of claim 1 wherein the hydrophilic polymer is selected from the group consisting of homopolymer of acrylic acid monomer, copolymers of acrylic acid;

vinyl polymer;

poly(ethylene oxide) polymers;

cellulose derivatives; and

the non-toxic, pharmaceutically acceptable salts of these polymers.

16. The composition of claim 15 wherein the hydrophilic polymer is an acrylic acid copolymer, the acrylic acid copolymer being present in an amount of approximately between 0.6 and 2 percent by weight of the composition.

17. The composition of claim 16 wherein the hydrophilic polymer is a salt of an organic amine selected from the group consisting of triethanolamine, diisopropanolamine, monoethanolamine, basic amino acids and amine surfactants and is present in an amount approximately between 0.3 and 10 percent by weight of the composition.

18. The composition of claim 17 wherein the bioactive agent is present in an amount between approximately 2 and 10 percent by weight of the composition.

19. The composition of claim 17 wherein the solvent system comprises a first, water-miscible organic solvent and a second, oil solvent present in an amount of up to approximately 30 percent by weight of the composition.

20. The composition of claim 1 wherein the bioactive agent is a drug.