Land O’Lakes Pharmaceutical Analysis Conference

Dissolution testing measures the rate of drug substance release into solution, impacting the extent of drug absorption. Drug manufacturers and regulatory agencies use dissolution testing to identify drug products that do not meet the desired clinical performance. Formulation composition and manufacturing processes can impact the material attributes of a drug product, which directly affect the dissolution mechanism. The dissolution method must be robust and sensitive in order to accurately measure these attributes. The establishment of dissolution specifications involves the creation of a test method as well as acceptance criterion driven by regulatory and internal expectations. Here, we will present the dissolution method development of a solid dispersion comprised of API and polymer. The compound is a modified (delayed) release drug product, designed to resist drug release in the stomach using a pH sensitive polymer in the solid dispersion, creating an amorphous solid solution with the API. Since the compound is a delayed release drug product, dissolution testing should adhere to USP <711> Dissolution for Delayed-Release Dosage Forms, which utilizes 0.1N HCl (pH 1) as the first stage acid medium. Early dissolution method development utilized 0.01N HCl (pH 2) as the first stage acid medium based on consistent drug release obtained in buffer stage. Continued dissolution method development of this compound focusing on the impact of the concentration of the acid media, optimization of surfactant level, particle size, and discriminatory power of the method will be presented. This development work will provide justification for selecting the appropriate dissolution method for further analytical development and commercialization of this drug product.