Competencies Consulting Services Drug Development
The necessary condition for the bioavailability of an orally administered solid drug is that it is in solution at the site of absorption. Therefore, the dissolution properties of an orally administered final dosage form (FDF) are of paramount importance for its efficacy and hence for formulation development and quality assurance. The dissolution rate of the active pharmaceutical ingredient (API) released from an FDF depends on the physical properties of FDF (its disintegration) and on its particle properties, in particular their particle size distribution (PSD). In addition, some excipients influence the dissolution behavior of API.
The production process of oral dosage forms includes different steps such as milling, drying, direct compression, wet- or dry- granulation of the materials and many more. Especially the tableting step has the potential to change the PSD of API- and excipient particles, since under pressure elastic- or plastic- deformation, aggregation, or fragmentation of particles with direct impact on the dissolution properties of particles may occur.
Accelsiors can offer help in the de-formulation process of brand products, by providing insight into the physicochemical properties of the API particles characterizing the dissolution behavior of the particles. This characterization is obtained by the analysis of dissolution time profiles using a developed mechanistic disintegration-dissolution model (DDM) employing mixed-effects nonlinear modeling 1, 2.
The developed method was deemed to be a first-principles approach to predict in vitro dissolution for pharmaceutical formulation and process development and for product release testing by the Dissolution Working Group of the International Consortium for Innovation and Quality in Pharmaceutical Development and of two focus groups of the American Association of Pharmaceutical Scientists: Process Analytical Technology (PAT) and In Vitro Release and Dissolution Testing (IVRDT) 3.
The offered characterization may also be useful for optimizing the generic formulations or for identification of products for bioequivalence studies, minimizing thus the risk of failing clinical studies 4. This minimization is based on revealing the differences in the formulations which may be present even when the dissolution factor, F2 > 50, indicates sufficient similarity of the dissolution profiles 4, 5.
In field of controlled release formulations (HPMC tablets) an analysis based on a deterministic prediction model (DPM) is available 6. Using that model a deep understanding of the effect of manufacturing conditions on the release properties of the API can be achieved.
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