Development and Validation of a Dissolution Test for Delayed Release Capsule Formulation of Duloxetine Hydrochloride

Navneet      Kumar; Dhanaraj      Sangeetha; Pingili      Sunil Reddy; Annarapu      Malleswara Reddy

Abstract

A dissolution test for duloxetine hydrochloride delayed release capsules was developed and validated according to current ICH and FDA guidelines. The discriminating dissolution test conditions and dissolution medium was chosen as 0.1 N HCl for acid stage and pH 6.8 buffer for buffer stage at a stirring rate of 100 rpm at 37.0°C using USP apparatus I (basket). A novel, rapid and sensitive isocratic reverse-phase HPLC method was developed for the analysis of in-vitro dissolution samples. In acidic medium, some portion of duloxetine hydrochloride degrades in to para-naphthol duloxetine and alpha-naphthol. The atomic mass numbers of degradation products formed in acidic medium were determined by LCMS/ MS. Separation of duloxetine from its major degradation impurities was achieved on Hypersil BDS C18 column (100mm x 4.6mm, 3 μm) using a 0.05 M phosphate buffer (pH 2.5)-acetonitrile (60:40 v/v) mobile phase at 40°C. The compounds were eluted isocratically at a flow rate of 1.0 mL/min and detection UV wavelength of 215 nm. In acid stage, the total % release of duloxetine was calculated as a sum of released % duloxetine and equivalent % of duloxetine converted into para-naphthol duloxetine and alpha-naphthol. During validation, standard curve was found to have a linear relationship (r > 0.998) over the analytical range of 0.02-7.5 μg/mL for acidic stage and 1.8-90 μg/mL for buffer stage. Accuracy ranged from 95 to 105 % and precision was < 2.5 % at all levels. The HPLC method was successfully applied for the screening of dissolution medium, determination of discriminatory power of dissolution test and the analysis of in-vitro dissolution samples of marketed duloxetine hydrochloride capsules.

Keywords: Development, Discriminating, Dissolution, Duloxetine, Capsules, HPLC-UV, LC-MS/MS, RRF, Validation, HPTLC