Preparation of Amorphous Solid Dispersions by Cryomilling: Chemical and Physical Concerns Related to Active Pharmaceutical Ingredients and Carriers
| Autor: | Robin Koekoekx, Emiel Michiels, Guy Van den Mooter, Timothy Pas, Bjorn Vergauwen, Joost Schymkowitz, Christian Clasen, Frederic Rousseau, Alessandra Bergonzi |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
food.ingredient
Materials science Drug Compounding Indomethacin Pharmaceutical Science 02 engineering and technology 030226 pharmacology & pharmacy Gelatin Cinnarizine 03 medical and health sciences 0302 clinical medicine food Hypromellose Derivatives Naproxen Drug Stability Fenofibrate Drug Discovery Spectroscopy Fourier Transform Infrared Transition Temperature Active ingredient Drug Carriers Molecular Structure Viscosity Povidone Serum Albumin Bovine 021001 nanoscience & nanotechnology Decomposition Dynamic Light Scattering Amorphous solid Molecular Weight Chemical engineering Solubility Molecular Medicine Glass 0210 nano-technology Crystallization |
| Zdroj: | Molecular pharmaceutics. 17(3) |
| ISSN: | 1543-8392 1001-1013 |
| Popis: | In this work, a chemical (and physical) evaluation of cryogenic milling to manufacture amorphous solid dispersions (ASDs) is provided to support novel mechanistic insights in the cryomilling process. Cryogenic milling devices are considered as reactors in which both physical transitions (reduction in crystallite size, polymorphic transformations, accumulation of crystallite defects, and partial or complete amorphization) and chemical reactions (chemical decomposition, etc.) can be mechanically triggered. In-depth characterization of active pharmaceutical ingredient (API) (content determination) and polymer (viscosity, molecular weight, dynamic vapor sorption, Fourier transform infrared spectroscopy, dynamic light scattering, and ANS and thioflavin T staining) chemical decomposition demonstrated APIs to be more prone to chemical degradation in case of presence of a polymer. A significant reduction of the polymer chain length was observed and in case of BSA denaturation/aggregation. Hence, mechanochemical activation process(es) for amorphization and ASD manufacturing cannot be regarded as a mild technique, as generally put forward, and one needs to be aware of chemical degradation of both APIs and polymers. ispartof: MOLECULAR PHARMACEUTICS vol:17 issue:3 pages:1001-1013 ispartof: location:United States status: published |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|