Emily G Benson, Dana E Moseson, Shradha Bhalla, Fei Wang, Miaojun Wang, Kai Zheng, Pravin K Narwankar, Lynne S Taylor
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Dissolution of copovidone-based amorphous solid dispersions: Influence of atomic layer coating, hydration kinetics, and formulation.
Atomic layer coating (ALC) is an emerging, solvent-free technique to coat amorphous solid dispersion (ASD) particles with a nanolayer ceramic coating that has been shown to improve powder characteristics and limit drug crystallization. Herein, we evaluate the impact of aluminum oxide coatings with varying thickness and conformality on the release behavior of ritonavir/copovidone ASDs. Release performance of powders, neat tablets, and formulated tablets was studied. Confocal fluorescence microscopy (CFM) was used to visualize particle hydration and phase separation during immersion of the ASD in aqueous media. CFM revealed particle hydration requires defects for solvent penetration, but coatings, regardless of thickness, had minor impacts on powder dissolution provided defects were present. In tablets where less surface area is exposed to the dissolution media due to gel formation, slowed hydration kinetics resulted in phase separation of the drug from the polymer in coated samples, limiting release. Formulation with two superdisintegrants, crospovidone and croscarmellose sodium, as well as lactose achieved ∼90% release in less than 10 minutes, matching the uncoated ASD particles of the same formulation. This study highlights the importance of hydration rate, as well as the utility of confocal fluorescence microscopy to provide insight into release and phase behavior of ASDs.
期刊介绍:
The Journal of Pharmaceutical Sciences will publish original research papers, original research notes, invited topical reviews (including Minireviews), and editorial commentary and news. The area of focus shall be concepts in basic pharmaceutical science and such topics as chemical processing of pharmaceuticals, including crystallization, lyophilization, chemical stability of drugs, pharmacokinetics, biopharmaceutics, pharmacodynamics, pro-drug developments, metabolic disposition of bioactive agents, dosage form design, protein-peptide chemistry and biotechnology specifically as these relate to pharmaceutical technology, and targeted drug delivery.