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pH-Dependent dissolving nano- and microparticles for improved peroral delivery of a highly lipophilic compound in dogs.
- Source :
- AAPS Journal; Mar2001, Vol. 3 Issue 1, p92-99, 8p
- Publication Year :
- 2001
-
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<subscript>0–48h</subscript> of 6.5 μg.h/mL and coefficient of variation (CV) of 116%) and much higher T<subscript>max</subscript>, as compared to both pH-sensitive formulations. With respect to exposure and interindividual variability, nanoparticles were superior to microparticles (AUC<subscript>0–48h</subscript> 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 15507416
- Volume :
- 3
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- AAPS Journal
- Publication Type :
- Academic Journal
- Accession number :
- 50532421
- Full Text :
- https://doi.org/10.1208/ps030108