Development and Validation of a USP Apparatus IV Dissolution Method for Dexamethasone in a Povidone-Iodine Ophthalmic Suspension

Research Article

Abstract

The exact in vitro characterization of complex ophthalmic formulations is an analytical challenge, particularly for suspensions containing active ingredients with divergent physicochemical properties. This study details the development and validation of a robust dissolution testing method using the USP Apparatus IV (flow-through cell) for Dexamethasone (0.1%) within a dual-drug ophthalmic suspension also containing Povidone-Iodine (0.6%). Traditional dissolution techniques often fail to provide physiologically relevant shear forces or adequate hydrodynamic stability for such formulations. Consequently, a method was optimized utilizing a phosphate buffer (pH 7.4) supplemented with 0.1% β -Cyclodextrin. While theoretical sink conditions are achievable in standard buffers, the inclusion of β-Cyclodextrin was critical to enhance wettability, prevent adsorption of the hydrophobic steroid to the apparatus tubing, and ensure method robustness. A 100KD cellulose ester membrane was employed to retain the suspension while facilitating the diffusion of dissolved analytes. Quantification was performed via a specific HPLC method using an ACE Excel 5 C8 column. The method showed superior discriminatory capability across various critical process parameters, including particle size distribution and viscosity modifications. Validation per ICH Q2(R2) guidelines confirmed the method's linearity (r² > 0.999), precision (%RSD < 2.0%), and accuracy (98.5–101.5%). These results indicate that the developed flow-through cell method is a viable quality control tool for ensuring the consistency and performance of multiphasic ophthalmic dosage forms.