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.
Otto H. York Department of Chemical Engineering, New Jersey Institute of Technology, 371 Tiernan Hall, University Heights, Newark, NJ 07102, USA.
Qiuxi
Q
Fan
Kamalesh K
KK
Sirkar
Yiping
Y
Wang
Bozena
B
Michniak
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