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pH-Dependent dissolving nano- and microparticles for improved peroral delivery of a highly lipophilic compound in dogs

De Jaeghere, Fanny
Galli, B.
Steulet, A. F.
Müller, I.
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Published in AAPS PharmSci. 2001, vol. 3, no. 1, p. 92-99
Abstract RR01, a new highly lipophilic drug showing extremely low water solubility and poor oral bioavailability, has been incorporated into pH-dependent dissolving particles made of a poly(methacrylic acid-co-ethylacrylate) copolymer. The physicochemical properties of the particles were determined using laser-light-scattering techniques, scanning electron microscopy, high-performance liquid chromatography, and x-ray powder diffraction. Suspension of the free drug in a solution of hydroxypropylcellulose (reference formulation) and aqueous dispersions of pH-sensitive RR01-loaded nanoparticles or microparticles were administered orally to Beagle dogs according to a 2-block Latin square design (n=6). Plasma samples were obtained over the course of 48 hours and analyzed by gas chromatography/mass spectrometry. The administration of the reference formulation resulted in a particularly high interindividual variability of pharmacokinetic parameters, with low exposure to compound RR01 (AUC<sub>0–48h</sub> of 6.5 μg.h/mL and coefficient of variation (CV) of 116%) and much higher T<sub>max</sub>, as compared to both pH-sensitive formulations. With respect to exposure and interindividual variability, nanoparticles were superior to microparticles (AUC<sub>0–48h</sub> of 27.1 μg.h/mL versus 17.7 μg.h/mL with CV of 19% and 40%, respectively), indicating that the particle size may play an important role in the absorption of compound RR01. The performance of pH-sensitive particles is attributed to their ability to release the drug selectively in the upper part of the intestine in a molecular or amorphous form. In conclusion, pH-dependent dissolving particles have a great potential as oral delivery systems for drugs with low water solubility and acceptable permeation properties.
Keywords NanoparticlesMicroparticlesOral AdministrationPoor Water SolubilityPH-Sensitive Polymer
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Other version: http://link.springer.com/10.1208/ps030108
Research group Technologie pharmaceutique
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DE JAEGHERE, Fanny et al. pH-Dependent dissolving nano- and microparticles for improved peroral delivery of a highly lipophilic compound in dogs. In: AAPS PharmSci, 2001, vol. 3, n° 1, p. 92-99. https://archive-ouverte.unige.ch/unige:79070

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Deposited on : 2016-01-11

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