Progesterone-loaded chitosan microspheres: a long acting biodegradable controlled delivery system.
Smooth, highly spherical, crosslinked chitosan microspheres in the size range of 45-300 microns loaded with progesterone were prepared by glutaraldehyde crosslinking of an aqueous acetic acid dispersion of chitosan containing progesterone in a non-aqueous dispersion medium consisting of liquid paraffin and petroleum ether stabilized using sorbitan sesquioleate. In vitro release of the drug into phosphate buffer at 37 degrees C was determined as a function of crosslinking density of the microspheres and particle size. The extent of drug release had a remarkable dependence on the crosslinking density of the microspheres, the highly 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 microsphere formulation by intramuscular injection in rabbits showed that a plasma concentration of 1 to 2 ng/ml was maintained up to 5 months without a high 'burst effect'. Data obtained suggest that the crosslinked chitosan microspheres would be an interesting system for long term delivery of steroids.
Division of Polymer Chemistry, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, India.
S R
SR
Jameela
T V
TV
Kumary
A V
AV
Lal
A
A
Jayakrishnan
D000818:Animals; D001673:Biodegradation, Environmental; D001682:Biological Availability; D002686:Chitin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D048271:Chitosan; D016503:Drug Delivery Systems; D008297:Male; D008863:Microspheres; D011374:Progesterone / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011817:Rabbits
D002686:Chitin; D011374:Progesterone; D048271:Chitosan