CONTROLLED DRUG DELIVERY FROM A NOVEL INJECT ABLE IN SITU FORMED BI OJJEGRADABLE

A novel method for in situ preparation of injectable biodegradable microspheres from the copolymer poly(lactide-co-glycolide) (PLGA) without incorporating unacceptable organic solvents is described. The delivery system is a dispersion of PLGA microglobules ("premicrospheres " or "embryonic microspheres") in an acceptable vehicle mixture (continuous phase) and whose integrity is maintained by use of appropriate stabilizers. A solution of PLGA. triacetin, drug, PEG 400, and Tween 80 (Oil Phase 1) are added dropwise with continuous homogenization to miglyol 812-Span 80 solution (Oil Phase 2), thereby inducing phase separation (coacervation) of PLGA and forming PLGA microglobules (containing the drug) dispersed in the continuous phase. This novel drug delivery system (NDDS) is a dispersion and has a viscous consistency but is sufficiently syringeable. When injected, it comes in contact with water from aqueous buffer or physiological fluid and as a result, the microglobules harden to form solid matrix type microparticles entrapping the drug (in sit