A comprehensive discussion on analytical method development and validation of a USP type-IV dissolution method for dexamethasone in a combination ophthalmic suspension with povidone-iodine

Abstract

Antimicrobial resistance resulting from the widespread use of topical antibiotics has accelerated the need for non-antibiotic strategies in ocular therapy. Povidone-iodine (PVP-I) offers broad antimicrobial activity without inducing resistance, while dexamethasone provides potent anti-inflammatory effects, making their combination a promising ophthalmic suspension for infectious and inflammatory conditions. To ensure therapeutic consistency, in-vitro dissolution testing is critical for suspension of Dexamethasone, as it characterizes drug release, supports formulation optimization, and provides evidence for regulatory bio-waivers. This investigation was carried out to develop and validate a USP Type-IV flow-through cell method (closed-loop configuration) for assessing the in-vitro release behavior of dexamethasone (0.1%) from povidone-iodine (0.6%) and dexamethasone (0.1%) ophthalmic suspension. The current dissolution method employed phosphate buffer (pH 7.4) with 0.1% β-cyclodextrin as medium, chosen for solubility, stability, and sink condition. A 100 kDa cellulose ester membrane enabled controlled diffusion. Chromatographic separation was performed on an ACE Excel-5 C8 column (250 × 4.6 mm, 5 µm) using an isocratic mobile phase of 0.6% β-cyclodextrin in water and acetonitrile (1:1 v/v). Partial validation per ICH Q2(R2) confirmed excellent linearity (r² > 0.999), precision (%RSD < 2.0), accuracy (98.5–101.5%), and solution stability for 72 h. The method was discriminatory for formulation changes and suitable for routine and stability testing of ophthalmic suspensions.