In vitro delivery of doxycycline hydrochloride based on a porous membrane-based aqueous-organic partitioning system

Qiuxi Fan, Kamalesh K. Sirkar, Yiping Wang, Bozena Michniak

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

This work investigated the controlled release of an antibiotic drug, doxycycline HCl, from its solution/suspension in an organic solvent in a reservoir through a porous membrane employing aqueous-organic partitioning with or without a mouse skin to simulate a skin patch. The reservoir contained the agent in solution in the solvent 1-octanol or its dispersion/solution in the solvent mineral oil with or without an enhancer. The porous membranes employed with water-in-pores were hydrophobic Celgard® 2400 of polypropylene and hydrophilized polyvinylidene fluoride (PVDF). Conventional Franz diffusion cells as well as a skin patch were used. The transport rates of the agent observed through both Celgard® and PVDF membranes could be successfully described by Fickian diffusion through the water-filled pores when the appropriate organic-aqueous partition coefficient was incorporated. The light mineral oil-based system yielded much higher permeability due to the much lower organic-aqueous partition coefficient of the antibiotic in light mineral oil. The optimized skin patch systems yielded drug flux and permeability values similar to their relevant membrane systems. The addition of a mouse skin beneath the patch drastically reduced the drug transfer rate. Among a number of enhancers used to correct this deficiency, linoleic acid at 10% level in the reservoir solution was found to yield a flux of 2.7±0.5 μg/cm 2 h and a permeability of 2.7e-04±5.0e-05 cm/h. These values are higher than the values available in literature obtained with full thickness human cadaver skin.

Original languageEnglish (US)
Pages (from-to)355-365
Number of pages11
JournalJournal of Controlled Release
Volume98
Issue number3
DOIs
StatePublished - Aug 27 2004

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

Keywords

  • Aqueous-organic partitioning
  • Controlled release
  • Doxycycline hydrochloride
  • Microporous and skin membranes
  • Patch
  • Suspension

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