Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

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

Evren Algın-Yapar^1,2 , Nuray Arı³, Tamer Baykara¹

¹Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Ankara, 06100 Tandogan Ankara; ²The Ministry of Health of Turkey, Turkish Medicines and Medical Devices Agency, SÃ¶gÃ¼tÃ¶zÃ¼ Mahallesi 2176. Sokak No:5, 06520 Ã‡ankaya Ankara; ³Department of Pharmacology, Faculty of Pharmacy, University of Ankara, 06100 Tandogan Ankara, Turkey.

For correspondence:- Evren Algın-Yapar Email: evren.yapar@yahoo.com Tel:+905323825686

Received: 14 December 2013 Accepted: 21 February 2014 Published: 24 March 2014

Citation: Algın-Yapar E, Arı N, Baykara T. Evaluation of In vitro and In vivo Performance of Granisetron In situ Forming Implants: Effect of Sterilization, Storage Condition and Degradation. Trop J Pharm Res 2014; 13(3):319-325 doi: 10.4314/tjpr.v13i3.1

© 2014 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

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 µg/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, Biocompati