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.
Jameela
S R
SR
Division of Polymer Chemistry, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, India.
Kumary
T V
TV
Lal
A V
AV
Jayakrishnan
A
A
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