Optimization of rifampicin encapsulation in PLGA polymeric reservoirs

Abstract

Rifampicin is one of the most commonly used antibiotics for treating tuberculosis, but shows low bioavailability and requires long-term administration, and hence its use may result in severe side effects. Encapsulation of rifampicin in polymeric reservoirs allows it to be administered locally and improves its pharmacological action. High rifampicin loading is crucial for obtaining an adequate therapeutic effect. Generally, the drug loading is a complex function of reservoir fabrication parameters. In the current work, we systematically varied the drug (rifampicin), polymer (PLGA) and dispersed phase contents as well as the solvent evaporation rate, particle size and number of particle washing cycles to characterize the challenges involved in encapsulating rifampicin. Physical insight into the low encapsulation efficiencies was provided, as well as an optimization of fabrication conditions to achieve higher drug loading levels. The particle solidification stage was found in the current work to be the most crucial step, where a significant amount of rifampicin was lost enhanced by its solubility in the aqueous medium. Increases in polymer concentration, solvent evaporation rate and particle size each significantly improved the drug loading by hindering of solvent-assisted escape of the drug. Based on our observation of the drug loading being extremely sensitive to the particle recovery and washing procedure after the solvent evaporation, most of the encapsulated rifampicin was concluded to be located on or very near the reservoir surface. Encapsulation could be significantly improved by fabricating multiple emulsions, especially double w/o/w emulsions, but the resultant particles were relatively large and porous, which might be a drawback for drug administration.

Keywords: Encapsulation; PLGA; Particles; Rifampicin.