Evaluation of In vitro and In vivo Performance of Granisetron In situ Forming Implants: Effect of Sterilization, Storage Condition and Degradation

  • E Algin-Yapar
  • N Ari
  • T Baykara
Keywords: Implant, Poly(DL-lactide-co-glycolide), Granisetron, Gamma irradiation, Sterilization, Degradation, Viscosity, Stability, Pharmacokinetic, Biocompatibility.

Abstract

Purpose: To investigate the effect of various solvent systems and gamma irradiation on the in vitro and in vivo performance of granisetron HCl injectable phase-sensitive in situ forming implants (ISFIs).
Methods: ISFIs were prepared by mixing and sterilized by gamma  irradiation. Effect of solvent system was studied. Injectability, polymer degradation and stability studies (4 and 25 oC for 4 months), viscosity
measurements, as well as in vitro and in vivo (in rabbits) drug release, and also histological examinations for biocompatibility studies (in rabbits and rats) were carried out.
Results: ISFIs showed good injectability from 20-gauge needle and their in vitro drug release increased in the following rank order of solvent/solvent combinations: dimethylsulphoxide (DMSO) > DMSO:prophylenecarbonate (PC) > DMSO:triacetin(TA) > DMSO:benzylbenzoate (BB). DMSO:PC incorporating ISFI gave zero order (r2 = 0.9503) drug release for 21 days; application of gamma irradiation accelerated drug release with a difference factor (f1) of 53 but zero order release (r2 = 9690) was maintained. Following test results for DMSO:PC including ISFI as decrease in molecular weight of polymer was descriptive for drug release behavior and  sterilization effect, additionally dynamic viscosities decreased in line with polymer degradation and all forms of this ISFI showed plastic flow
(fresh, irradiated, aged at 4 and 25 oC for 4 months). In vivo performance showed steady state plasma drug concentrations between 2 to 21 days with value of 0.55 ± 0.03 ìg/ml and biocompatibility was confirmed by  histological results obtained at specific stages of tissue reactions, and also by lack of fibrous capsule formation.
Conclusion: An ISFI for long-term antiemetic therapy achieved in this  preliminary study is promising and, therefore, further investigations are required.


Keywords: Implant, Poly(DL-lactide-co-glycolide), Granisetron, Gamma irradiation, Sterilization, Degradation, Viscosity, Stability, Pharmacokinetic, Biocompatibility.

Published
2014-05-26
Section
Articles

Journal Identifiers


eISSN: 1596-9827
print ISSN: 1596-5996