In vitro delivery of doxycycline hydrochloride based on a porous membrane-based aqueous-organic partitioning system.
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 microg/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.
Fan
Qiuxi
Q
Otto H. York Department of Chemical Engineering, New Jersey Institute of Technology, 371 Tiernan Hall, University Heights, Newark, NJ 07102, USA.
Sirkar
Kamalesh K
KK
Wang
Yiping
Y
Michniak
Bozena
B
D000544:Alzheimer Disease; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D003692:Delayed-Action Preparations; D004058:Diffusion; D004318:Doxycycline / Q000008:administration & dosage*; D016503:Drug Delivery Systems; D066298:In Vitro Techniques; D019787:Linoleic Acid / Q000737:chemistry; D008297:Male; D008567:Membranes, Artificial; D051379:Mice; D008812:Mice, Hairless; D008899:Mineral Oil; D000442:Octanols / Q000737:chemistry; D010539:Permeability; D011126:Polypropylenes; D012869:Skin Absorption; D012996:Solutions
D000900:Anti-Bacterial Agents; D003692:Delayed-Action Preparations; D008567:Membranes, Artificial; D000442:Octanols; D011126:Polypropylenes; D012996:Solutions; D008899:Mineral Oil; D019787:Linoleic Acid; D004318:Doxycycline