PROGESTERONE-LOADED CHITOSAN MICROSPHERES - A LONG-ACTING BIODEGRADABLE CONTROLLED DELIVERY SYSTEM

Smooth, highly spherical, crosslinked chitosan microspheres in the siz e range of 45-300 mu m loaded with progesterone were prepared by gluta raldehyde crosslinking of an aqueous acetic acid dispersion of chitosa n containing progesterone in a non-aqueous dispersion medium consistin g of liquid paraffin and petroleum ether stabilized using sorbitan ses quioleate. Ln vitro release of the drug into phosphate buffer at 37 de grees C was determined as a function of crosslinking density of the mi crospheres and particle size. The extent of drug release had a remarka ble dependence on the crosslinking density of the microspheres, the hi ghly crosslinked spheres releasing only around 35% of the incorporated steroid in 40 days compared to 70% from spheres lightly crosslinked. Determination of the in vivo bioavailability of the steroid from micro sphere formulation by intramuscular injection in rabbits showed that a plasma concentration of 1 to 2 ng/ml was maintained up to 5 months wi thout a high 'burst effect'. Data obtained suggest that the crosslinke d chitosan microspheres would be an interesting system for long term d elivery of steroids, (C) 1998 Elsevier Science B.V.