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Original Research Article
Evaluation of In vitro
and In vivo Performance of Granisetron In situ
Forming Implants: Effect of Sterilization, Storage
Condition and Degradation
Evren Algın-Yapar1,2*,
Nuray Arı3 and Tamer Baykara1
1 Department of
Pharmaceutical Technology, Faculty of Pharmacy,
University of Ankara, 06100 Tandogan Ankara, 2The
Ministry of Health of Turkey, Turkish Medicines and
Medical Devices Agency, Sögütözü Mahallesi 2176. Sokak No:5, 06520
Çankaya
Ankara, 3Department
of Pharmacology, Faculty of Pharmacy, University of
Ankara, 06100 Tandogan Ankara, Turkey
*For correspondence:
Email:
evren.yapar@yahoo.com,
algin@pharmacy.ankara.edu.tr
Tel: +90. 532. 382 56 86, Fax: +90. 312.
218 35 85
Received: 14 December 2013
Revised accepted:21
February 2014
Tropical Journal of
Pharmaceutical Research, March 2014;
13(3):
319-325
http://dx.doi.org/10.4314/tjpr.v13i3.1
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 ħ
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, Biocompatibility. |
