Title: Development of a long-acting injectable formulation with nanoparticles of rilpivirine (TMC278) for HIV treatment
Authors: Baert, Lieven ×
van 't Klooster, Gerben
Dries, Willy
François, Marc
Wouters, Alfons
Basstanie, Esther
Iterbeke, Koen
Stappers, Fred
Stevens, Paul
Schueller, Laurent
Van Remoortere, Pieter
Kraus, Guenter
Wigerinck, Piet
Rosier, Jan #
Issue Date: Aug-2009
Publisher: Wissenschaftliche Verlagsgesellschaft
Series Title: European Journal of Pharmaceutics and Biopharmaceutics vol:72 issue:3 pages:502-8
Abstract: Long-acting parenteral formulations of antiretrovirals could facilitate maintenance and prophylactic treatment in HIV. Using the poorly water- and oil-soluble non-nucleoside reverse transcriptase inhibitor (NNRTI) TMC278 (rilpivirine) as base or hydrochloride (HCl), nanosuspensions were prepared by wet milling (Elan NanoCrystal technology) in an aqueous carrier. Laser diffraction showed that the average particles size were (1) close to the targeted size proportionality (200-400-800 nm), with increasing distributions the larger the average particle size, and (2) were stable over 6 months. Following single-dose administration, the plasma concentration profiles showed sustained release of TMC278 over 3 months in dogs and 3 weeks in mice. On comparison of intramuscular and subcutaneous injection of 5mg/kg (200 nm) in dogs, the subcutaneous route resulted in the most stable plasma levels (constant at 25 ng/mL for 20 days, after which levels declined slowly to 1-3 ng/mL at 3 months); 200 nm nanosuspensions achieved higher and less variable plasma concentration profiles than 400 and 800 nm nanosuspensions. In mice, the pharmacokinetic profiles after a single 20mg/kg dose (200 nm) were similar with two different surfactants used (poloxamer 338, or d-alpha-tocopheryl polyethylene glycol 1000 succinate). In conclusion, this study provides proof-of-concept that 200-nm sized TMC278 nanosuspensions may act as long-acting injectable.
ISSN: 0939-6411
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Non-KU Leuven Association publications
× corresponding author
# (joint) last author

Files in This Item:

There are no files associated with this item.

Request a copy


All items in Lirias are protected by copyright, with all rights reserved.

© Web of science