Vollmer U, Müller B W, Peeters J, Mesens J, Wilffert B, Peters T
Janssen Research Foundation, Germany.
J Pharm Pharmacol. 1994 Jan;46(1):19-22. doi: 10.1111/j.2042-7158.1994.tb03713.x.
2-Hydroxypropyl-beta-cyclodextrin (HP-beta-CyD) and 2,6-dimethyl-beta-cyclodextrin (D-beta-CyD) were studied for transdermal penetration enhancement of the cytochrome P450 inhibitor liarozole by an in vivo transdermal absorption rat model. The mode of action of penetration enhancement was investigated by differential scanning calorimetry (DSC). In-vivo, HP-beta-CyD, as a 20% aqueous solution, increased the absorption of liarozole approximately threefold and a 20% aqueous solution of D-beta-CyD decreased the percutaneous absorption of liarozole in blood by a factor of 0.6. However, pretreatment with D-beta-CyD (20%, 4 h) enhanced the transdermal absorption 9.4-fold. In the DSC experiments the thermal profile of human stratum corneum was practically unchanged after treatment with HP-beta-CyD, but treatment with D-beta-CyD revealed an interaction of D-beta-CyD with the protein and lipid fraction. Thus the results from DSC and those from the permeability experiments revealed that D-beta-CyD acts as a transdermal absorption enhancer by changing the stratum corneum barrier whereas HP-beta-CyD influences the partitioning behaviour of the drug in the skin.
通过体内透皮吸收大鼠模型，研究了2-羟丙基-β-环糊精（HP-β-CyD）和2,6-二甲基-β-环糊精（D-β-CyD）对细胞色素P450抑制剂利阿唑的透皮渗透增强作用。采用差示扫描量热法（DSC）研究了渗透增强的作用方式。在体内，HP-β-CyD作为20%的水溶液，使利阿唑的吸收增加了约三倍，而20%的D-β-CyD水溶液使血液中利阿唑的经皮吸收降低了0.6倍。然而，用D-β-CyD（20%，4小时）预处理可使透皮吸收提高9.4倍。在DSC实验中，用HP-β-CyD处理后人角质层的热谱基本未变，但用D-β-CyD处理显示D-β-CyD与蛋白质和脂质部分存在相互作用。因此，DSC结果和渗透性实验结果表明，D-β-CyD通过改变角质层屏障起透皮吸收促进剂的作用，而HP-β-CyD影响药物在皮肤中的分配行为。
