DRUG MICROENCAPSULATION BY PLA PLGA COACERVATION IN THE LIGHT OF THERMODYNAMICS - 1 - OVERVIEW AND THEORETICAL CONSIDERATIONS/

Phase separation of poly(lactide) (PLA) and poly(lactide-co-glycolide) (PLGA), often called ''coacervation'' in the pharmaceutical field, is one of the classical methods for peptide drug microencapsulation in b iodegradable polyesters. Although numerous studies have used this tech nique, the underlying physicochemical mechanisms of polyester coacerva tion under conditions of microsphere production have not been well-des cribed yet. Moreover, the quality of microencapsulation in terms of dr ug loading efficiency and residual organic solvents is often not entir ely satisfactory and depends greatly on the specific drug and polymer used. The first part of this contribution reviews briefly the scientif ic and patent literature on PLA/PLGA coacervation. Then, the underlyin g physicochemical principles of polyester coacervation are discussed a nd relevant thermodynamic models presented. More specifically, attempt s were made to clarify the necessary characteristics of polymers, solv ents, and coacervating and hardening agents for successful phase separ ation and microsphere formation. These basic considerations may contri bute to a better understanding of the boundary conditions crucial for efficient drug microencapsulation by polyester coacervation.