Biodegradable Progesterone Microsphere Delivery System for Osteoporosis Therapy

Abstract

The purpose of this study was to formulate and characterize a controlled-release biodegradable delivery system of progesterone for the treatment or prevention of osteoporosis. Microspheres of progesterone were formulated using copolymers of poly(glycolic acid-co-dl-lactic acid)(PGLA 50/50 and PGLA 15/85) and poly(L-lactic acid)(L-PLA) of similar molecular weight by the emulsion solvent evaporation technique. The effects of process variables, such as volume fraction, polyvinyl alcohol (PVA) concentration, polymer composition, and stir speed during preparation, on the yield, encapsulation efficiency (EEF), particle size distribution, in vitro release profiles of progesterone, and surface morphology of progesterone microspheres were investigated. Increasing the volume fraction from 9% to 22% increased the EEF without significantly increasing the yield; however, the rate of progesterone release from the microspheres decreased. Increasing the PVA concentration from 1% to 5% had no significant influence on the EEF, but the rate of progesterone release from microspheres increased. Polymer composition had no significant effect on the EEF, but had a significant effect on the particle size distribution, surface morphology, and release rate of progesterone from the microspheres. Stir speed did not have a significant influence on the EEF; however, stir speed influenced particle size distribution and the rate of progesterone release from microspheres of the same sieve-size range. The results suggest that controlled release of progesterone is possible by varying the different process variables, and that PGLA 50/50 provided the slowest release of progesterone. This should provide a means of delivering progesterone for months for the treatment or prevention of osteoporosis in postmenopausal women.

Key Words:

• Biodegradable
• Microspheres
• Osteoporosis
• Progesterone
• Solvent evaporation