Elucidation of Rate-determining Step in Dissolution Process of Oral Sustained-Release Formulations by Direct Observation

Abstract

The sustained-release formulations consist of many components, such as the active pharmaceutical ingredient, excipient, binder, lubricant, and polymer, leading to the complex dissolution process. The objective of this study is the elucidation of the rate-determining step in the dissolution process by direct optical observation. The composite particles of hydroxypropyl methylcellulose (HPMC) and brilliant blue FCF (model drug) were prepared, and the direct observation of the dissolution process and image analysis were conducted. The decrease in particle size and the penetration of solvent into the particles during the dissolution process had little impact on the sustained-release performance. On the other hand, the diffusion rate of the model drug in the HPMC gel strongly depended on the type of HPMC, suggesting that the rate-determining step in the dissolution process of the sustained-release formulations using HPMC would be the drug diffusion process in the polymer gel in the particles.