Formulation for controlled release of drugs by combining hydrophilic and hydrophobic agents

Abstract

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 substantially constant rate of release for an extended period of time.

What is claimed is:  
     
         1 . An implant for 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 therapeutically active agent at a concentration from 10 to 50 weight percent of the implant;    a release modulator at a concentration from 10 to 50 weight percent of the implant;    wherein said therapeutically active agent is released within a therapeutic dosage which does not vary by more than about 100% for a period of at least about 3 days.    
     
     
         2 . An implant according to  claim 1 , wherein said release modulator is a hydrophilic entity and said therapeutically active agent is a hydrophobic entity.  
     
     
         3 . An implant according to  claim 2 , wherein said release modulator is hydroxypropylmethylcellulose.  
     
     
         4 . An implant according to  claim 1 , wherein said release modulator is a hydrophobic entity and said therapeutically active agent is a hydrophilic entity.  
     
     
         5 . An implant according to  claim 1 , wherein said release modulator is a therapeutically active agent.  
     
     
         6 . An implant according to  claim 5 , wherein said active agent is a steroid and said release modulator is a water soluble antibiotic.  
     
     
         7 . An implant according to  claim 5 , wherein said active agent is a non-steroidal antiinflammatory drug and said release modulator is a water soluble antibiotic.  
     
     
         8 . An amplant according to  claim 1 , wherein said biodegradable polymer is poly-lactate glycolic acid copolymer.  
     
     
         9 . An implant for sustained drug release comprising: 
 poly-lactate glycolic acid copolymer at a concentration of at least about 20 weight percent of the implant;    methotrexate at a concentration from 10 to 50 weight percent of the implant;    ciprofloxin at a concentration from 10 to 50 weight percent of the implant;    wherein said methotrexate is released within a therapeutic dosage which does not vary by more than about 100% for a period of at least about 3 days.