Decoding of API particle size in reference market product for bio-equivalent and cost effective generic product development

Abstract

Decoding or deformulation involves the characterization of the reference listed drug innovator drug where the most important step in deformulation is solid state characterization of API (Active pharmaceutical ingredient). Bioavailability and dissolution rate are directly impacted by API particle-size distribution. It aids in ensuring a bioequivalent formulation, particularly for medications with bioavailability that are dissolution-sensitive. Therefore, the information obtained from the innovator product's API's particle-size distribution is crucial for assuring solubility and bioequivalence. When a generic drug manufacturer experiences multiple Bioequivalence (BE) failures during the development of their product, it can lead to increased developmental costs and ultimately increased product cost the patients. The manufacturer may need to conduct additional studies and testing to optimize the formulation, which can be time-consuming and expensive. Therefore, it's critical to lower the chance of BE failures in order to lower the price of creating generic medicines and the financial burden on patients. Here conventional particle size determination methods are not useful, hot stage microscopy (HSM) is an ideal method , which can be beneficial with microscopic capturing of melting events in the melting point ranges of API and excipients components in a tablet dosage form. In this study, Xarelto 20 mg film-coated tablet was the reference product used and by using hot stage microscopy method, particle size distribution of reference API was found to be 77.4μ and Accordingly, the Rivaroxaban API particles are to be engineered for generic product design and development to have similar particle size distributions based on D90 and D50 values decoded from the reference market product. This can be useful to ensure similar drug performance and efficacy and ultimately favours the bioavailability and would be accessible to low cost as compare to the respective reference product.