Understanding curing of ethylcellulose film coating and in vitro in vivo performance of oral dosage forms with scientific regulatory implications on biowaiver.

摘要

The aim of this study focus on the extended release formulation on two aspects: the quantification and mechanistic research on pharmaceutical coating curing with a specific focus on how the moisture affect the curing; and in vivo and in vitro release of matrix ER tablets with implications on regulatory biowaiver using marketed products as practical examples. In all cases, it was found that the relative humidity of the environments were more important to reach higher extent of coalescence for EC pseudolatex films and temperature along cannot achieve sufficient polymer coalescence. A quantitative relationship was established that could be used to quantify the extent of coalescence in EC curing to a reasonable accuracy. The NIR spectral data with the tool of chemometrics can enable accurate prediction of physicomechanical properties accurately. Dissolution models demonstrated the release mechanism of EC coated ER multiparticulate was predominately determined by the breaking down of the coating rather than diffusion of drugs through the EC coating layer. Fluoresence anisotropy was found to be useful in the solid system for the first time. By measuring fluorescence anisotropy in the fluorescence labeled EC films can allow real time monitoring of the curing process. To justify biowaiver, it is essential to understand effects of API properties, formulation design, product characteristics, test method and its in vivo relevance. It is therefore concluded that the biowaiver criteria specified in the regulatory guidance should apply only to multiparticulate beaded dosage forms where strengths only differ in the number of beads containing the active moiety.