Formulation for controlled release of drugs by combining hyrophilic and hydrophobic agents
Combinations of hydrophilic and hydrophobic entities in a biodegradable sustained release implant are shown to modulate each other's rate of release. Formulations of a therapeutically active agent and modulator provide controlled, sustained release for an extended period of time.
1. An implant for controlled, sustained drug release comprising:
a pharmacologically acceptable biodegradable polymer which is degraded at the site of implantation, wherein said biodegradable polymer comprises at least about 20 weight percent of the implant;
a first therapeutically active agent at a concentration from 10 to 50 weight percent of the implant;
a release modulator comprising hydroxy-propylmethylcellulose at a concentration from 10 to 50 weight percent of the implant, and said release modulator further comprising a second therapeutically active agent having a different activity than the first therapeutically active agent;
wherein said implant is an anhydrous solid structure which is degraded at the site of implantation and releases said first therapeutically active agent within a therapeutic dosage which does not vary by more than about 100% for a period of at least about 3 days after implantation;
wherein said anhydrous solid structure is a particle, sheet, plaque, fiber, microcapsule or disc.
2. An implant according to claim 1 , wherein said first therapeutically active agent is a steroid and said second therapeutically active agent is a water soluble antibiotic.
3. An implant according to claim 1 , wherein said first therapeutically active agent is a non-steroidal antiinflammatory drug and said second therapeutically active agent is a water soluble antibiotic.
4. An implant according to claim 1 wherein said biodegradable polymer is poly-lactic acid glycolic acid copolymer.
5. An implant for controlled, sustained drug release comprising:
poly-lactic acid glycolic acid copolymer at a concentration of at least about 20 weight percent of the implant;
a therapeutically active antiinflammatory drug at a concentration from 10 to 50 weight percent of the implant;
a release modulator comprising hydroxy-propylmethylcellulose at a concentration from 10 to 50 weight percent of the implant said release modulator further comprising a second therapeutically active agent having a different activity than the antiinflammatory drug;
wherein said implant is an anhydrous solid structure which releases said therapeutically active antiinflammatory within a therapeutic dosage that does not vary by more than about 100% for a period of at least about 3 days.
6. An implant for controlled, sustained drug release comprising:
poly-lactic acid glycolic acid copolymer at a concentration of at least about 20 weight percent of the implant;
a therapeutically active steroid at a concentration from 10 to 50 weight percent of the implant;
a release modulator comprising hydroxy-propylmethylcellulose at a concentration from 10 to 50 weight percent of the implant, and said release modulator further comprising a second therapeutically active agent having a different activity than the steroid;
wherein said implant is an anhydrous solid structure which is degraded at the site of implantation and releases said therapeutically active steroid within a therapeutic dosage which does not vary by more than about 100% for a period of at least about 3 days after implantation.
7. An implant according to claim 6 , wherein said anhydrous solid structure is a particle, sheet, patch, plaque, fiber, microcapsule or disc.
8. An implant according to claim 6 wherein said second therapeutically active agent is a hydrophilic compound.
9. An implant according to claim 8 wherein said second therapeutically active agent is a water soluble antibiotic.
10. An implant for controlled, sustained drug release comprising:
poly-lactic acid glycolic acid copolymer at a concentration of at least about 20 weight percent of the implant;
a therapeutically active non-steroidal anti-inflammatory drug at a concentration from 10 to 50 weight percent of the implant;
a release modulator comprising hydroxy-propylmethylcellulose at a concentration from 10 to 50 weight percent of the implants and the release modulator further comprising a second therapeutically active agent having a different activity than the therapeutically active non-steroidal anti-inflammatory drug;
wherein said implant is an anhydrous solid structure which releases said therapeutically active non-steroidal anti-inflammatory drug within a therapeutic dosage which does not vary by more than about 100% for a period of at least about 3 days after implantation.
11. An implant according to claim 10 , wherein said second therapeutically active agent is a hydrophilic compound.
12. An implant according to claim 11 , wherein said second therapeutically active agent is a water soluble antibiotic.