Development and evaluation of in situ gel forming system for sustained delivery of cyclosporine.
Phase-sensitive in situ gel forming controlled release formulations of cyclosporine were prepared using poly (lactide-co-glycolide) and a solvent system consisting of various proportions of benzyl benzoate and benzyl alcohol. Uniformity of content of cyclosporine in the formulation and in vitro release samples was determined by radio immune assay (RIA). FTIR and CD spectroscopy ratified the conformational stability of cyclosporine in the formulation and in vitro release samples, respectively. Rheological properties of the formulations, assessed under isothermal conditions, showed dilatant behavior of all the formulations. In vivo studies were carried out on the optimized formulations vis-à-vis pure cyclosporine in rats and drug levels were monitored for 13 days. Mean plasma concentration of cyclosporine was calculated for all the animals and pharmacokinetic parameters were determined using Win NonLin software. The studies construed better regulation of plasma drug levels with the optimized formulation vis-à-vis routine once-a-day administration of cyclosporine. The subcutaneous tissues, further subjected to histopathological examinations ascertained the biocompatibility of the formulation.
Dhawan
Sanju
S
University Institute of Pharmaceutical Sciences (UGC Centre of Advanced Studies), Panjab University, Chandigarh 160 014, India. sanjudhawan@rediffmail.com
Kapil
Rishi
R
Kapoor
Deepak N
DN
Kumar
Manoj
M
D000818:Animals; D001565:Benzoates / Q000737:chemistry; D019905:Benzyl Alcohol / Q000737:chemistry; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D016572:Cyclosporine / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems / Q000379:methods*; D004355:Drug Stability; D005782:Gels; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics; D007279:Injections, Subcutaneous; D008297:Male; D044367:Phase Transition; D011098:Polyglactin 910 / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D012212:Rheology; D012995:Solubility; D014783:Viscosity
D001565:Benzoates; D003692:Delayed-Action Preparations; D005782:Gels; D007166:Immunosuppressive Agents; D011098:Polyglactin 910; D016572:Cyclosporine; D019905:Benzyl Alcohol; C006723:benzyl benzoate