Structure-Property Relationships Of PLA Microspheres Controlled Delivery And Modeling

Biodegradable polymeric microspheres, as a new type of controlled drug delivery system, have advantages of controlled release of active drug molecules over prolonged time to target sites, easiness of administration, favorable biocompatibility, and good degradability. In consideration of hydrophobic nature, some drug composites are encapsulated in polymeric microspheres at highly dispersed amorphous state to improve solubility and bioavailability. Structure-property relationships of the microsphere system are investigated in this work from both of microscopic mechanism and macroscopic mass transfer phenomena with experiments and modeling. Nifedipine, a calcium antagonist for treatment of hypertension, was studied as a model hydrophobic ingredient for drug entrapment and release. An oil-in-water solvent evaporation method was used to prepare polymer microspheres with controlled size. Fundamental mechanism of drug release was investigated from three aspects: interaction between molecules of drugs and polymers, morphology and dispersion of drugs, and in vitro release experimental findings. Taking consideration of effects of diffusion, finite dissolution rate, and moving front of dissolution, a new model is developed for quantitative description of the release patterns. Finally, integrated with pharmacokinetics, the release model was extended to in vivo process to evaluate drug concentration levels in the plasma.Nifedipine loaded microspheres were prepared using biodegradable polymers poly(D,L-lactide) (PLA) and poly(D,L-lactide-co-glycolide) (PLGA). Microspheres size, entrapment efficiency, morphology, and release profiles were characterized by DLS, SEM, DSC, FTIR and in vitro release tests. Particle size was controlled with interfacial tension and viscosity of polymer and surfactant (PVA) concentrations. Diameters of microspheres vary from 1μm to 10μm. A broad range of drug release profiles were achieved. Due to large surface area, drug leakage is found in small particles, as a result of diffusion to continuous phase during fabrication. Compromise has to be made between high entrapment efficiency and small size. For all the microspheres, nifedipine was found to be totally amorphous in the polymer, which suggested that the drug is well dispersed in the matrix.