A Review on Dissolution Method Development for Drug Products: Current Regulations and Prospects

Abstract

Dissolution (in vitro release) testing has been the subject of intense scientific and regulatory interest over the past several decades. As an analytical methodology, in vitro dissolution testing measures drug release into the dissolution media. The U. S. Food and Drug Administration (USFDA) Dissolution Database was reviewed and screened regarding the type of dosage forms, apparatus type, agitation speed, media volume, and recommended time points for the dissolution profile. The dissolution method requires special laboratory equipment, following a well-defined protocol. Basic information is available in the United States Pharmacopeia general chapters<711> Dissolution, <724> Drug Release, and <1092> The Dissolution Procedure – Development and Validation and these chapters were used as a starting point for this revision. The article describes current regulatory expectations for establishing a suitable dissolution method for implementing quality control tools, a way to maintain lot quality and consistency between development batches and post-approval commercial batches. Dissolution methods draw offers some advantages as a possible surrogate for extensive clinical studies in certain cases required after scale-up and post-approval changes in the product's life cycle and serves as an essential tool for establishing waivers for filing of lower strengths of the drug product. The step-by-step dissolution method development plan as per current regulatory perspectives and the factors to be considered are explained with examples. Scientist requires detailed insights on the selection of media and volumes, physicochemical properties of active substance, sink condition, type of enzymes, selection of apparatus, deaeration, sinkers, agitation speed, and time point’s measures. The advanced dissolution method is evaluated against its discriminatory power by intentionally varying formulation and process variables