Effect of Formulation Variables on the Release of Letrozole from Natural Biodegradable Polymeric Implants.

ABSTRACT

Aim: Letrozole, a non-steroidal aromatase inhibitor, prevents the body from producing its own estrogen. The objective of the present study was to explore the fabrication and evaluation of natural biodegradable polymeric Letrozole implant for long term drug release targeting postmenopausal women with metastatic breast cancer. Methodology: The effect of different formulation variables i.e. different types of excipients and different hardening times (6 hrs, 12 hrs and 24 hrs) with exposure to formaldehyde vapour was investigated on drug loading efficiency and drug release profile. The result of in-vitro dissolution study was fitted to different kinetic models to evaluate the kinetic data. Results: Letrozole release was studied for 10 to 19 days with some excipients. The in vitro Letrozole release from Gelatin-Sodium Alginate biodegradable polymeric implant was maximum, about 19 days, where Cetyl alcohol was incorporated as excipient. The release kinetics was explored and explained using Higuchi, zero and first order while the mechanism of release was confirmed with Korsmeyer-peppas model. Implants were found to follow Higuchi model the best in most cases. Good correlations were also obtained with Korsmeyere-Peppas model. According to these models, the drug released from implants were of diffusion controlled, where the drug was found to leave the matrix through pores and channels formed by entry of dissolution medium. Conclusion: The addition of different excipients and variation in hardening times were found to influence the drug loading efficiency and drug release significantly. Further investigation would confirm its potential in breast cancer therapy.