Structure-based strategy for consistency evaluation of dosage forms / 药学学报

ABSTRACT

Strategies and techniques are extremely important to improve the evaluation efficiency and fully guarantee the consistency of dosage forms. For preparations with a structural feature as solid dosage forms and particulate dispersion systems, the structures of dosage forms are the outcome of the specific formulation and production process, which determine the drug delivery behaviors as well as the pharmacokinetics of the dosage forms. Conventional techniques failed to quantitatively determine the structures of dosage forms. Synchrotron radiation micro-computed tomography is a new generation of structural quantitative characterization technology in revealing the internal structure of dosage forms with unprecedented capability for quantitative characterization of the static and dynamic structures of dosage forms, enabling to reversely analyze the production process and identify the structure differences between the generics and brand products. Based on synchrotron radiation micro-computed tomography methodology researches and applications in static structures (powders, particulate systems, tablets, films, membranes, etc.), dynamic structures (hydration) and de-formulation of production process, we have classified the structures of dosage forms into four levels from macro-scope to molecular level as dosage forms, granular intermediates for formulation, dynamic structure and molecular structures, and proposed dosage form structure based new strategy for consistency evaluation. Along with conventional dissolution/ release behavior similarity, the internal structure consistency ensures high consistency between the brand product and the generics.