Preparation of (hydrophilic) INZ/PLGA particles (microcapsules) employing a unique frozen water phase — investigation of optimal formulation

摘要

In this study, poly (lactide-co-glycolide) (PLGA)-based particles loaded with a low-molecular-weight hydrophilic drug (isoniazid; INZ, [Mw] = 137) in a liquid–liquid system were prepared. Briefly, this involved preparing PLGA particles after freezing an inner water phase containing INZ, the composition of the water and oil phases in the water-in-oil 1 + oil 2 in oil 3 (w/(o_1 +o_2)/o_3) emulsion was then carefully examined to improve our understanding about controlling the size, drug loading efficiency, and morphology of the prepared PLGA particles. Initially, we examined the effects of different oil phases, cyclohexane (CyH) solution dissolving oil- soluble surfactant (o_1 phase), dichloromethane (DCM) solution dissolving PLGA (o2 phase), and DCM/CyH solution dissolving an oil-soluble surfactant (o3 phase), on the prepared multiple emulsion. Further, we examined the effects of the composition of the inner water phase containing INZ as a model low- molecular-weight hydrophilic drug. The composition of the oil phase did not have a marked effect on the size or drug loading efficiency of the prepared INZ/PLGA particles. Irregularly shaped INZ/PLGA particles were occasionally obtained by varying the composition of the oil phase. Such particles were not favorable for demonstrating random drug release behavior from the interior of the PLGA particles. Results showed that the composition of the inner water phase had a significant effect on the size and drug loading efficiency of the INZ/PLGA particles, the obtained particles were spherical. Thus, the size, drug loading efficiency, and morphology of the INZ/PLGA particles prepared using the emulsion technique, which involves freezing of the inner water phase, could be controlled by varying the composition of the inner water phase.