Role of crystallization in the phase inversion dynamics and protein release kinetics of injectable drug delivery systems.

The role of polymer crystallization in the phase inversion dynamics and in vitro protein release kinetics of semi-crystalline poly (epsilon-caprolactone) and amorphous poly (D,L-lactide) (PDLA) blend solutions has been examined using high performance liquid chromatography (HPLC), scanning electron microscopy (SEM), and differential scanning calorimetry (DSC) techniques. Varying the degree of crystallizability of the solutions led to the emergence of two general classes of depots. Depots with a high degree of crystallinity are characterized by porous morphologies indicative of solid-liquid (s--l) de-mixing and delayed burst release profiles. Alternatively, depots with a low degree of crystallinity are characterized by dense morphologies formed by mild liquid-liquid (l--l) phase separation and slow, uniform protein release rates. An interpretation of these results in terms of a qualitative model for the protein release mechanism is also given.