Development and evaluation of novel biodegradable transdermal penetration enhancers

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This studies were aimed to develop the transdermal therapeutic system of highly ionizable drugs by ion pair formation with novel biodegradable counter ions.The following results were obtained.(1) Novel biodegradable triglycerides having quaternary ammonium group (YKS) were synthesized as counter ions for ion pair complexation with salicylate or cromoglicate (SCG) (model anionic drugs).The permeability of these anionic drugs through the rat skin was significantly increased by lipophilic ion pair formation in the presence of the YKS.(2) The biodegradability of YKS were illustrated by the pH-stability experiments.Judging from the primary irritation indices, YKS-21 had less cutaneous irritancy compared with Azone.(3) The combination of pretreatment with YKS and ion pair formation was more effective for ion pair transport.(4) The maximum flux and permeability coefficient of SCG from SCG-YKS ion pair in propylene glycol/isopropyl alcohol/isopropyl myristate(15 : 75 : 1O)were about 15 and 3 times respectively higher than those of SCG alone in the same vehicle mixture.(5) The plasma concentrations after topical application to the rat were simulated using obtained permeation and disposition parameters.Although there were some differences in the time course patterns, it was found that the percutaneous penetration of SCG was increased by ion pair formation with YKS in vivo as well.The results of this study suggest that it may be possible through the selection of appropriate counter ions to improve the efficiency of transdermal penetration of other highly ionized drugs, and that ion pair formation is an important consideration in the formulation of ionized drugs.