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J Pharm Sci. 2019 Jan;108(1):525-537. doi: 10.1016/j.xphs.2018.11.026. Epub 2018 Nov 22.

Characterization of the Partition Rate of Ibuprofen Across the Water-Octanol Interface and the Influence of Common Pharmaceutical Excipients.

Author information

1
NCE Formulation Sciences, Drug Product Development, AbbVie Inc., North Chicago, Illinois 60064.
2
NCE Formulation Sciences, Drug Product Development, AbbVie Inc., North Chicago, Illinois 60064. Electronic address: ping.gao@abbvie.com.

Abstract

This work reports the measurement of the partition rate of a model drug, ibuprofen (IBU), from aqueous solutions into octanol in the absence and presence of common pharmaceutical excipients including glucose, lactose, maltoheptaose, hydroxypropyl methylcellulose, polyvinylpyrrolidone, polyvinylpyrrolidone-vinyl acetate, hydroxypropyl methylcellulose AS, sodium dodecyl sulfate, Tween 80, and sodium taurocholate at varying concentrations. This attempts to assess the kinetic aspect of IBU partitioning across the water-octanol interface by applying a mechanistic model and to characterize the interfacial resistance. A significant reduction in Pi across the water-octanol interface was observed with extremely low concentration of the selected excipients in the aqueous media. These results reveal the presence of a surface excess of adsorbed excipients at the water-octanol interface. The retardation of the Pi of IBU was found to be sensitive to (1) the molecular weight or the degree of polymerization of these excipients, (2) the hydrodynamic condition of the experimental method, and (3) the pH of the aqueous media. Retardation of the Pi of IBU in the presence of excipients observed in this study is proposed by a steric obstruction mechanism through the adsorbed surface excess layer of excipients located at the water-octanol interface.

KEYWORDS:

2-phase dissolution; biomimetic; biorelevant; diffusion; dissolution test; interface; in vitro; partition; polymer; surfactant

PMID:
30471290
DOI:
10.1016/j.xphs.2018.11.026

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