Drug microencapsulation by PLA/PLGA coacervation in the light of thermodynamics. 2. Parameters determining microsphere formation

Journal of Pharmaceutical Sciences
C ThomasinBruno Gander

Abstract

Phase separation (frequently called coacervation) of poly(lactide) (PLA) and poly(lactide-co-glycolide) (PLGA) is a classical method for drug microencapsulation. Here, attempts have been made to describe this process in the light of thermodynamics. Different PLA/PLGAs were dissolved in either dichloromethane or ethyl acetate, phase separated by addition of the coacervating agent silicone oil (PDMS), and hardened in either octamethylcyclotetrasiloxane or hexane. Various stages of phase separation were defined microscopically, and the coacervate and continuous phases characterized with respect to volume, composition, polymer molecular weight, and rheological behavior. The optimal amount of PDMS was inversely proportional to the polymer molecular weight and hydrophilicity, and a coacervate viscosity of above 5-10 Pa s was required for stable coacervate droplets. The composition and, consequently, viscosity of the coacervate and continuous phases depended on the polymer-solvent-PDMS interactions, as analyzed by the parameters chi (Flory), delta (Hildebrand), and delta(int)E (Hô). In general, the lattice model of FIory and Scott describing polymer-polymer incompatibility best explained the results. The interaction parameters and vis...Continue Reading

Citations

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