Development and Validation of a RP-HPLC Method for Simvastatin Capsules

Flavia      Dias Marques-Marinho; Bruna      Diniz Freitas; Jose      Carlos da Costa Zanon; Ilka      Afonso Reis; Angelica      Alves Lima; Cristina      Duarte Vianna-Soares

Abstract

Simvastatin, a lipid-lowering agent of the statins class, is widely used in the treatment of hypercholesterolemia and in the prevention of cardiovascular diseases. Currently, simvastatin is available in the global market in both tablet and capsule forms. No official method has been reported for the assaying or dissolution testing of simvastatin capsules. Dissolution specifications were established to evaluate in vitro release studies for simvastatin capsules in this work. Adequate dissolution test conditions were obtained with 0.5% sodium dodecyl sulfate in 0.01 M monobasic sodium phosphate buffer at pH 7.0±0.05 (900 mL), and paddle agitation at 75 rpm for 45 min was used to investigate the immediate release (IR) of simvastatin capsules. Simvastatin quantified in the dissolution medium for capsules using the developed HPLC method, showed R2>0.98, selectivity (no placebo interference), precision (%RSD<5), recovery (95.0 to 105.0%) and robustness for deliberate changes in the buffer molarity and pH of the media and for different C8 columns (p value>0.05) according to the United States Pharmacopeia (2011) criteria. This work highlights the need to develop suitable dissolution conditions to establish criteria for the analysis of IR solid oral dosage form. The developed HPLC simvastatin quantitation method does not require the previous treatment of aliquots with manganese oxide, as described in the US Pharmacopeia and in the British Pharmacopoeia for ultraviolet spectroscopic methods.

Keywords: Capsules, Dissolution Validation, Liquid Chromatography, Reversed-phase, Simvastatin, Pharmacopoeia, immediate release, crystalline powder, biosynthesis, biological membrane permeability