Improving maraviroc oral bioavailability by formation of solid drug nanoparticles

European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V
Alison C SavageAndrew Owen

Abstract

Oral drug administration remains the preferred approach for treatment of HIV in most patients. Maraviroc (MVC) is the first in class co-receptor antagonist, which blocks HIV entry into host cells. MVC has an oral bioavailability of approximately 33%, which is limited by poor permeability as well as affinity for CYP3A and several drug transporters. While once-daily doses are now the favoured option for HIV therapy, dose-limiting postural hypotension has been of theoretical concern when administering doses high enough to achieve this for MVC (particularly during coadministration of enzyme inhibitors). To overcome low bioavailability and modify the pharmacokinetic profile, a series of 70 wt% MVC solid drug nanoparticle (SDN) formulations (containing 30 wt% of various polymer/surfactant excipients) were generated using emulsion templated freeze-drying. The lead formulation contained PVA and AOT excipients (MVCSDNPVA/AOT), and was demonstrated to be fully water-dispersible to release drug nanoparticles with z-average diameter of 728 nm and polydispersity index of 0.3. In vitro and in vivo studies of MVCSDNPVA/AOT showed increased apparent permeability of MVC, compared to a conventional MVC preparation, with in vivo studies in rats s...Continue Reading

Citations

Jul 23, 2019·Expert Opinion on Drug Delivery·Yuqing GongSantosh Kumar
Jan 7, 2020·Expert Opinion on Drug Metabolism & Toxicology·Miao MiaoGuangdi Li
Feb 23, 2020·Pharmaceutics·Florina-Daniela CojocaruCosmin-Teodor Mihai
Jan 14, 2021·Journal of Food Science·Khaing Zar MyintJie Shen
Feb 5, 2021·Clinical Pharmacology and Therapeutics·Aaron S Devanathan, Mackenzie L Cottrell
May 29, 2020·Journal of Controlled Release : Official Journal of the Controlled Release Society·Dhanashree H Surve, Anil B Jindal

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