Formulation and evaluation of Simvastatin injectable in situ implants

Abstract

Simvastatin is anti-hyperlipidemic drug which is used to control elevated cholesterol or hypercholesterolemia. The drug undergoes extensive first pass metabolism and has a t 1/2 of 3 h. It has poor bioavailability (about 5%) and high protein binding (>95%).The dosage form currently available is conventional uncoated tablet administered once daily. The objective of the present study was to improve the bioavailability of the drug by formulating an intraperitoneal implant and to sustain the drug release for atleast 15 days. The formulation was prepared by polymer precipitation method. In this method, the polymer drug solution is injected into the aqueous buffer from which the solvent dissipates into buffer and forms a solid implant. The optimized formulations were evaluated for drug content, cumulative percentage drug release, solvent ratio, surface morphology and drug interactions. From our studies, it was observed that the drug entrapment efficiency increased and the burst release decreased with increase in the polymer concentration. We could achieve sustained release of the drug with optimized formulation. The formulation with 20% polymer concentration exhibited moderate burst release and sustained release for 15 days. The in situ implants showed no drug polymer interactions. The SEM configurations showed polymer precipitation and the crosslinking of the polymer. Pharmacokinetic studies performed on rats confirmed sustained drug release up to 15 days. The bioavailability of the drug was also found to be improved and showed a 3 fold increase when compared to control tablets (ZOCOR 10 mg). Hence in addition to our studies, further research and clinical investigations can certainly help in proposing Simvastatin in situ implants as a treatment alternative in hyperlipidemic patients. © 2012 Academic Journals Inc.