Sustained release composition

• US 4,707,362 A
• Filed: 02/15/1985
• Issued: 11/17/1987
• Est. Priority Date: 02/15/1985
• Status: Expired due to Term

• Current Assignee: BioTex Incorporated
• Original Assignee: BioTex Incorporated
• Inventors: Nuwayser, Elie S.
• Primary Examiner(s): Schenkman, Leonard
• Application Number:
  US06/702,008
• Time in Patent Office: 1,005 Days
• Field of Search: 424/19, 424/433, 514/843, 514/967, 514/964, 514/965
• US Class Current: 424/433
• 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

Abstract

A vehicle which provides rapid release of a drug and prolonged release of a drug is disclosed.

Claims

1. A vaginal contraceptive having both rapid release and prolonged release of spermicide at effective concentrations, comprising:

a. a suppository body, comprising hydrophilic material which melts at or below the temperature of the vagina and having incorporated therein a spermicide, the spermicide being released therefrom at effective contraceptive concentrations within the first minute after placement of the contraceptive in the vagina; and

b. at least one film insert in the suppository body, the film insert comprising a water-soluble polymer which is bioerodible and having incorporated therein a spermicide which is released at effective contraceptive concentrations over a period of up to 24 hours after placement of the contraceptive in the vagina.

2. The vaginal contraceptive of claim 1 wherein the suppository body is comprised of hydrophilic material selected from the group consisting of polyethylene glycols, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene stearates and sorbitan fatty acid esters and the film insert is comprised of a water-soluble polymer selected from the group consisting of starches, dextrins, alginates, nature gums, gelatin, casein, agar, alkyl ethers of cellulose, hydroxyalkyl ethers of cellulose, alkyl ethers of starch, hydroxyalkyl ethers of starch, ionic starches, carboxylates, carboxymethyl cellulose, mixed ethers of starch, mixed ethers of cellulose, polyvinyl alcohols and polyvinyl pyrrolidone.

15. The vaginal contraceptive of claim 2 wherein the spermicide is selected from the group consisting of nonylphenoxypoly(ethyleneoxy) ethanol, octoxynol-9, menfegol, dodecaethylene glycol monolaurate, phenylmercuric acetate and phenylmercuric nitrate.

3. A vaginal contraceptive which releases effective contraceptive concentrations of a spermicide incorporated therein within the first minute after placement of the contraceptive in the vagina and for a period of up to 24 hours after placement of the contraceptive in the vagina, comprising:

a. a suppository body comprising a hydrophilic material which melts at or below the temperature of the vagina, a foaming agent and spermicide; and

b. at least one film insert within the suppository body, comprising polyvinyl alcohol or polyvinyl pyrrolidone, spermicide and a plasticizer, which releases the spermicide over a period of up to 24 hours after placement of the contraceptive in the vagina.

4. The vaginal contraceptive of claim 3, wherein polyethylene glycol is the hydrophilic material;

the foaming agent comprises (a) at least one alkali metal carbonate or at lease one alkali metal bicarbonate and (b) at lease one dicarboxylic acid, or salt thereof, or at least one polycarboxylic acid, or salt thereof, and the plasticizer is glycerin or propylene glycol, the vaginal contraceptive comprosing from about 60% to about 85% polyethylene glycol by weight;

from about 5% to about 15% by weight of at least one alkali metal carbonate or at least one alkali metal bicarbonate;

from about 5% to about 15% by weight of at least one dicarboxylic acid, or salt thereof, or at least one polycarboxylic acid, or salt thereof;

up to about 10% by weight of a spermicide;

from about 4% to about 8% by weight of polyvinyl alcohol or polyvinyl pyrrolidone; and

about 1.4% by weight of glycerin or propylene glycol.

5. The vaginal contraceptive of claim 4, which is comprised of polyethylene glycol 1450 and polyethylene glycol 1000 in a 1:

1 ratio;

the spermicide is nonoxynol-9;

about 1% by weight of sodium citrate;

about 9% by weight of tartaric acid;

about 8% by weight of sodium bicarbonate;

from about 5% to about 7% by weight of polyvinyl alcohol and from about 1% to about 2% by weight of glycerin.

6. A vaginal contraceptive having both rapid release and prolonged release of spermicide at effective contraceptive concentrations and having a suppository body which melts at or below the temperature of the vagina and at least one film within the suppository body which provides prolonged release of spermicide at effective concentrations, comprising about 67.2% by weight of polyethylene glycol;

about 7.4% by weight of a spermicide;

about 18.3% by weight of a foaming agent;

about 5.7% by weight of polyvinyl alcohol and about 1.4% by weight of a film plasticizer.

7. The vaginal contraceptive of claim 6 in which polyethylene glycol 1450 and polyethylene glycol 1000 are present in equal amounts;

the spermicide is nonoxynol-9; and

the foaming agent is comprised of sodium citrate, tartaric acid and sodium bicarbonate, the sodium citrate being present as approximately 0.9% of the total contraceptive weight, the tartaric acid being present as approximately 9.1% of the total contraceptive weight and the sodium bicarbonate being present as approximately 8.3% of the total contraceptive weight.

8. A vehicle for drug delivery which provides rapid release and sustained release of a drug, the vehicle comprised of:

a. a suppository body comprising hydrophilic material which melts at or below body temperature, the suppository body releasing a drug incorporated therin within the first minute after contact of the suppository body with an aqueous medium at body temperature; and

b. at least one film insert in the suppository body, the insert releasing a drug incorporated therein over a period of up to 24 hours after contact with an aqueous medium at body temperature.

9. A vehicle for drug delivery which provides rapid release and sustained release of a drug and which is inserted into a body cavity, the vehicle comprising:

a. a suppository body comprising a material which melts at the temperature of the body cavity and dispersed therethrough a drug, the material which melts at the temperature of the body cavity being selected from the group consisting of;

polyethylene glycols, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene stearates, and sorbitan fatty acid esters; and

b. at least one film insert comprising a material which slowly erodes at the temperature of the body cavity and a drug, the material which slowly erodes being selected from the group consisting of;

starches, dextrins, alginates, natural gums, gelatin, casein, agar, alkyl ethers of cellulose, hydroxyalkyl ethers of cellulose, alkyl ethers of starch, hydroxyalkyl ethers of starch, ionic starches, carboxylates, carboxymethyl cellulose, mixed ethers of starch, mixed ethers of cellulose, polyvinyl alcohols and polyvinyl pyrrolidone,

whereby, upon insertion into a body cavity, the suppository body provides rapid release of said drug and the film insert provides sustained release of said drug.

10. A method of making a vaginal contraceptive which is comprised of a suppository body which melts at or below the temperature of the vagina and at least one film within the suppository body having both rapid release and prolonged release of spermicide at effective contraceptive concentrations, comprising the steps of:

a. molding a suppository body comprised of a spermicide and polyethylene glycol;

b. making a film comprised of a spermicide and polyvinyl alcohol; and

c. incorporating a film formed in (b) into the body formed in (a).

11. A method of making a vaginal contraceptive which is comprised of a suppository body which melts at or below the temperature of the vagina and at least one film within the suppository body, having both rapid release and prolonged release of spermicide at effective contraceptive concentrations, comprising the steps of:

a. molding a suppository body comprising a hydrophilic polymer, a spermicide and a foaming agent;

b. making a film comprised of a water-soluble polymer, a spermicide and a film plasticizer; and

c. incorporating the film formed in (b) into the suppository body of (a).

12. A method of making a vaginal contraceptive which is comprised of a suppository body which melts at or below the temperature of the vagina and at least one film within the suppository body, having both rapid release and prolonged release of spermicide at effective contraceptive concentrations, comprising the steps of:

a. combining polyethylene glycol, nonoxynol-9 and a foaming agent to form a homogeneous mixture;

b. forming a suppository body by molding the homogeneous mixture;

c. combining polyvinyl alcohol nonoxynol-9 and a film plasticizer;

d. forming a film of the combination produced in (c); and

e. incorporating the film formed in (d) into the suppository formed in (b).

13. The method of claim 12 in which the polyethylene glycol is selected from the group consisting of polyethylene glycol 1450 and polyethylene glycol 1000;

the foaming agent is comprised of sodium citrate, tartaric acid and sodium bicarbonate; and

the film plasticizer is glycerin.

14. A method of making a vaginal contraceptive having both rapid release and prolonged release of spermicide at effective contraceptive concentrations, comprising the steps of:

a. forming a base mixture by melting polyethylene glycol 1450 and polyethylene glycol 1000 in a 1;

1 ratio;

b. cooling the base mixture;

c. combining cooled base bixture, nonoxynol-9 and a foaming agent in sufficient quantities to produce a combination comprising from about 50% by weight to about 60% by weight inclusive of cooled base mixture, from about 5% by weight to about 6% by weight, inclusive of nonoxynol-9 and about 20% by weight of a foaming agent;

d. molding the combination of (c) to form a suppository body;

e. combining about 67 wt % polyvinyl alcohol;

about 13 wt % glycerin and about 20 wt % nonoxynol-9;

f. forming a film of the combination produced in (d);

g. incorporating the film formed in (f) into the suppository body formed in (d); and

h. refrigerating the product formed in g. at a temperature of about 4°

C. for about 1 hour.