1. In Vitro Lipolysis Model to Predict Food Effect of Poorly Water-Soluble Drugs Itraconazole, Rivaroxaban, and Ritonavir.
- Author
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Patel RP, Cristofoletti R, Wu F, Shoyaib AA, and Polli JE
- Subjects
- Humans, Water chemistry, Administration, Oral, Models, Biological, Tablets, Itraconazole chemistry, Lipolysis drug effects, Ritonavir chemistry, Solubility, Food-Drug Interactions, Rivaroxaban chemistry, Rivaroxaban administration & dosage
- Abstract
It is desirable to predict positive food effect of oral formulations due to food mediated dissolution enhancement of lipophilic drugs. The objective was to assess the ability of in vitro lipolysis to anticipate a positive food effect. Tested formulations included rivaroxaban and itraconazole, where some formulations, but not all, exhibit a positive food effect in vivo in humans. Amorphous solid dispersion formulations of ritonavir, which exhibit a negative food effect in vivo in humans, were also studied. Fe-lipolysis and Fa-lipolysis media representing fed and fasted intestinal conditions were used. Results show frequent agreement between in vitro lipolysis predictions and in vivo human outcomes. For rivaroxaban, food effect of unformulated active pharmaceutical ingredient (API) and products were correctly predicted where 2.5 mg and 10 mg strengths did not show any food effect; however, 20 mg did show a positive food effect. For itraconazole, all four products were correctly predicted, with Sporanox, Sempera, and generic capsules having a food effect, but Tolsura not having a positive food effect. For ritonavir, lipolysis predicted a positive food effect for API and Norvir tablet and powder, but Norvir products have negative food effect in vivo in humans. Overall, the lipolysis model showed favorable predictability and merits additional evaluation., Competing Interests: Declaration of competing interest There are no conflicts of interest for these authors to declare. The information in the paper reflects views from authors and should not be construed to represent FDA's views or policies., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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