Rifampicin-loaded ‘flower-like’ polymeric micelles for enhanced oral bioavailability in an extemporaneous liquid fixed-dose combination with isoniazid

Authors
Moretton, Marcela Analía; Hötch, Christian; Taira, Carlos Alberto; Sosnik, Alejandro Dario
Publication Year
2014
Language
English
Format
article
Status
Published version
Description
BACKGROUND: Coadministration of rifampicin (RIF)/isoniazid (INH) is clinically recommended to improve the treatment of tuberculosis. Under gastric conditions, RIF undergoes fast hydrolysis (a pathway hastened by INH) and oral bioavailability loss. AIM: We aimed to assess the chemical stabilization and the oral pharmacokinetics of RIF nanoencapsulated within poly(ε-caprolactone)-b-PEG-b-poly(ε-caprolactone) 'flower-like' polymeric micelles. MATERIALS & METHODS: The chemical stability of RIF was evaluated in vitro under acid conditions with and without INH, and the oral pharmacokinetics of RIF-loaded micelles in rats was compared with those of a suspension coded by the US Pharmacopeia. RESULTS: Nanoencapsulation decreased the degradation rate of RIF with respect to the free drug. Moreover, in vivo data showed a statistically significant increase of RIF oral bioavailability (up to 3.3-times) with respect to the free drug in the presence of INH. CONCLUSION: Overall results highlight the potential of this nanotechnology platform to develop an extemporaneous liquid RIF/INH fixed-dose combination suitable for pediatric administration.
Fil: Moretton, Marcela Analía. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina
Fil: Hötch, Christian. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina
Fil: Taira, Carlos Alberto. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Sosnik, Alejandro Dario. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Technion - Israel Institute of Technology; Israel. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina
Subject
PEDIATRIC TUBERCULOSIS
LIQUID FIXED DOSE COMBINATION (FDC)
RIFAMPICIN CHEMICAL STABILIZATION
FLOWER-LIKE POLYMERIC MICELLE
IMPROVED ORAL PHARMACOLKINECTICS
Otras Nanotecnología
Nanotecnología
INGENIERÍAS Y TECNOLOGÍAS
Access level
Restricted access
License
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repository
CONICET Digital (CONICET)
Institution
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identifier
oai:ri.conicet.gov.ar:11336/16124