USE OF SOLUBILITY PARAMETERS OF DRUG AND VEHICLE TO PREDICT FLUX THROUGH SKIN
USE OF SOLUBILITY PARAMETERS OF DRUG AND VEHICLE TO PREDICT FLUX THROUGH SKIN
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DOI：
10.1111/1523-1747.ep12696635
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发表时间：
1986-08-01
影响因子：
6.5
通讯作者：
FLOWERS, FP
中科院分区：
文献类型：
--
作者：
SLOAN, KB;KOCH, SAM;FLOWERS, FP
茶碱在肉豆蔻酸异丙酯、辛醇、二甲基甲酰胺、丙二醇、乙二醇和甲酰胺中的溶解度和通过皮肤的通量已通过实验测定。对应于各个通量的实验渗透系数（Kp）的值由通量/溶解度= Kp确定，然后将其与由已知的载体（δ v）、茶碱（δ i）和皮肤（δ s）的溶解度参数计算的各个理论分配系数（PC）的值进行比较。对于溶解度参数在δ v = 12-18（cal/cm 3）1/2范围内的载体，理论log PC - 2.52 =实验log Kp具有良好的相关性。这允许从计算的理论分配系数和实验确定的溶解度在该范围内确定相对通量。对于溶解度参数在δ v = 8- 1/2（cal/cm 3）1/2范围内的载体或载体混合物，与从δ v = 1/2 -18（cal/cm 3）1/2范围内的结果预测的那些相比，通量和渗透系数大幅增加，由于这些载体的溶解度参数与皮肤的溶解度参数相似而引起的载体对皮肤的影响。发现质量、通量和渗透系数与药物在载体中的溶解度成反比，其最小值大致对应于δ i = δ v的点。
The solubilities of theophylline in, and fluxes through skin from, isopropyl myristate, octanol, dimethylformamide, propylene glycol, ethylene glycol, and formamide have been determined experimentally. Values for experimental permeability coefficients (Kp) corresponding to the respective fluxes were determined from, flux/solubility = Kp, which were then compared with values for the respective theoretical partition coefficients (PC) calculated from the known solubility parameters for the vehicles (.delta.v), theophylline (.delta.i) and skin (.delta.s). There was a good correlation for theoretical log PC - 2.52 = experimental log Kp for vehicles exhibiting solubility parameters in the range of .delta.v = 12-18 (cal/cm3)1/2. This allows relative fluxes to be determined from calculated theoretical partition coefficients and experimentally determined solubilities in that range. For vehicles or mixtures of vehicles exhibiting solubility parameters in the range of .delta.v = 8-12 (cal/cm3)1/2 large increases in fluxes and permeability coefficients, compared with those predicted from the results in the .delta.v = 12-18 (cal/cm3)1/2 range, were observed because of vehicle effects on the skin caused by the similarity in solubility parameters of those vehicles to that of skin. Qualitatively, fluxes and permeability coefficients were found to be inversely dependent on drug solubility in the vehicles with a minimum that corresponded approximately to the point where .delta.i = .delta.v.