Abstract
The in vitro release behavior of a novel liposome-based drug delivery device has been characterized. The system consists of a molded agarose matrix in which the model drug (progesterone) was dispersed either free or associated with one of four lipid formulations: egg-phosphatidylcholine (EPC) liposomes, EPC/cholesterol (2:1) liposomes, Intralipid® emulsion, and dipalmitoylphosphatidylcholine (DPPC) liposomes. Drug release rates from the devices into aqueous buffer were measured at 37° C. The free progesterone release rate decreased rapidly over 24 h with over 90% delivered. The liposomal patches, on the other hand, imposed apparent zero-order kinetics: for example, both the EPC and DPPC systems delivered their progesterone payloads at about 1%/h over 24 h. Further, the EPC and DPPC patches significantly slowed transdermal drug delivery across excised hairless mouse skin. The EPC device retarded throughput to one-half the control value, the DPPC system reduced the transport kinetics by an order of magnitude. The results support two hypotheses: (a) the liposomal-based reservoir system can modulate drug input via the skin, (b) the zero-order release of progesterone from liposomes is determined by slow interfacial transport out of the bilayer into the surrounding aqueous medium.
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