Monolithic LC method applied to fesoterodine fumarate low dose extended-release tablets: Dissolution and release kinetics

Abstract

A dissolution test for fesoterodine low dose extended-release tablets using liquid chromatographic (LC) method equipped with a C₁₈ monolithic column was developed and validated. LC system was operated isocratically at controlled temperature (40 °C) using a mobile phase of acetonitrile:methanol:0.03 M ammonium acetate (pH 3.8) (30:15:55, v/v/v), run at a flow rate of 1.5 mL/min and detected at 208 nm. The best dissolution conditions for this formulation were achieved using a USP apparatus 2 (paddle) at 100 rpm and 900 mL of phosphate buffer at pH 6.8 as the dissolution medium. Validation parameters such as the specificity, linearity, accuracy, precision, and robustness were evaluated according to international guidelines, giving results within the acceptable range. The kinetic parameters of drug release were also investigated using model-dependent methods and the dissolution profiles were best described by the Higuchi model. The validated dissolution test can be applied for quality control of this formulation.

Keywords: Dissolution test; Fesoterodine; Low dose extended-release tablets; Monolithic LC; Release kinetics.

Fig. 1

Chemical structure of fesoterodine fumarate.

Fig. 2

Chromatograms of fesoterodine reference solution with UV spectra (A) and placebo sample solution (B) in dissolution medium. Chromatographic conditions: Phenomenex Onyx C₁₈ monolithic column (100 mm×4.6 mm i.d.), 40 °C; mobile phase: acetonitrile:methanol:0.03 M ammonium acetate (pH 3.8) (30:15:55, v/v/v); flow rate: 1.5 mL/min; detection: 208 nm.

Fig. 3

Dissolution profile of fesoterodine low dose extended-release tablets (n=6) in phosphate buffer pH 6.8 medium (37±0.5 °C) using apparatus 2 rotating at 100 rpm.

Fig. 4

Graphical plots obtained by fitting experimental release data of fesoterodine to (A) zero-order, (B) first-order, (C) Higuchi, (D) Hixson–Crowell, and (E) Korsmeyer–Peppas models. R², coefficient of determination; k, dissolution constants of respective mathematical models.