Fabrication, characterization and in vitro release of paclitaxel (Taxol®) loaded poly (lactic-co-glycolic acid) microspheres prepared by spray drying technique with lipid/cholesterol emulsifiers

Abstract

Spray dry technique was applied to produce paclitaxel loaded microspheres of biodegradable poly (lactic-co-glycolic acid) (PLGA) as an alternative delivery system. Various emulsifiers such as L-α-dipalmitoyl-phosphatidylcholine (DPPC), cholesterol, polyvinyl alcohol (PVA), gelatin were incorporated in order to achieve high encapsulating efficiency of paclitaxel in the microspheres and desired properties for a sustained release. Atomic force microscopy (AFM) and scanning electron microscopy (SEM) showed that the surface of the microspheres with high ratio of lipid was spherical and smooth. Those made with other emulsifiers had rougher surface with pores. Incorporation of lipid, cholesterol or gelatin can significantly increase the drug content in the microspheres. The differential scanning calorimetry (DSC) result indicated that the paclitaxel trapped in the microspheres existed in an amorphous or disordered-crystalline status in the polymer matrix. The zeta potential of the microspheres was negative in general and was strongly influenced by the type of the emulsifiers used in fabrication. The system formulated with cholesterol was most stable. The release profiles of various formulations with PVA, gelatin as well as low ratio of DPPC showed almost zero-order release kinetics in the first 3 weeks after an initial burst less than 5% in the first day. The release rate then gradually decreased. The microspheres fabricated with high ratio of DPPC exhibited large initial burst. When cholesterol was combined together with DPPC as an emulsifier, the release became faster. © 2001 Elsevier Science B.V. All rights reserved.