Solid/Hollow Depots for Drug Delivery, Part 1: Effect of Drug Characteristics and Polymer Molecular Weight on the Phase-Inversion Dynamics, Depot Morphology, and Drug Release

摘要

The objective of this research was to evaluate the effect of drug characteristics and polymer molecular weight (MW) on phase-inversion dynamics, depot morphology, and drug release in injectable in situ depot-forming drug delivery systems. Two poly(lactide-co-glycolide) (50:50) polymers with different MW (RG502 and RG504) and two drugs with different hydrophilicity (metoclopramide salt and metoclopramide base) were studied here. The drug release from injectable depots, the polymer MW changes, and the cross-sectional depot morphologies were investigated, respectively. The results show that the initial drug release from high-MW polymer RG504 was always faster than that from low-MW polymer RG502, regardless of the drug type. Interestingly, depot morphology shows the development of a hollow core for RG502, whereas RG504 forms a solid core. The relationship of the depot morphology to release kinetics is proposed based on these observations. The use of basic drug catalyzes polymer degradation, during processing and over time. These affect starting MW and subsequent MW, and the effect on release kinetics is consistent with the general effects of MW. This research suggests that the polymer MW is an important effect on the polymer phase inversion kinetics, and thus the resultant depot morphology.