Lee B J, Cui J H, Parrott K A, Ayres J W, Sack R L
Biological Rhythm and Controlled Release Lab., College of Pharmacy, Kangwon National University, Chuncheon, Korea.
Arch Pharm Res. 1998 Oct;21(5):503-7. doi: 10.1007/BF02975365.
Percutaneous absorption and model membrane variations of melatonin (MT) in aqueous-based propylene glycol and 2-hydroxypropyl-beta-cyclodextrin vehicles were investigated. The excised hairless mouse skin (HMS) and two synthetic ethylene vinyl acetate (EVA) and microporous polyethylene (MPE) were selected as a model membrane. The solubility of MT was determined by phase equilibrium study. The vertical Franz type cell was used for diffusion study. The concentration of MT was determined using reverse phase HPLC system. The MT solubility was the highest in a mixture of PG and 2-HP beta CD. The percutaneous absorption of MT through excised HMS increased as the solubility increased. However, the permeability coefficient decreased and then slightly increased in a mixture of PG and 2-HP beta CD. On the other hand, both flux and permeability coefficient through EVA membrane decreased as the solubility increased. No MT was detected over 12 h after starting diffusion through MPE membrane. The flux of MT was dependent on the type of membrane selected. Flux of MT was greatest in excised HMS followed by EVA and MPE membrane. Flux of MT through EVA membrane was 5-20 times lower when compared to excised HMS. Interestingly, volumes of donor phase when MPE membrane was used, significantly increased during the study period. The HMS might be applicable to expect plasma concentration of MT in human subjects based on flux and pharmacokinetic parameters as studied previously. The current studies may be applied to deliver MT transdermally using aqueous-based vehicles and to fabricate MT dosage forms.
研究了褪黑素（MT）在水基丙二醇和2-羟丙基-β-环糊精载体中的经皮吸收及模型膜变化。选用切除的无毛小鼠皮肤（HMS）以及两种合成的乙烯醋酸乙烯酯（EVA）和微孔聚乙烯（MPE）作为模型膜。通过相平衡研究测定MT的溶解度。采用垂直式Franz扩散池进行扩散研究。使用反相高效液相色谱系统测定MT的浓度。MT在PG和2-HPβ-CD的混合物中溶解度最高。随着溶解度增加，MT通过切除的HMS的经皮吸收增加。然而，在PG和2-HPβ-CD的混合物中，渗透系数先降低后略有增加。另一方面，随着溶解度增加，通过EVA膜的通量和渗透系数均降低。开始通过MPE膜扩散12小时后未检测到MT。MT的通量取决于所选膜的类型。MT在切除的HMS中的通量最大，其次是EVA膜和MPE膜。与切除的HMS相比，MT通过EVA膜的通量低5至20倍。有趣的是，使用MPE膜时，供体相的体积在研究期间显著增加。基于之前研究的通量和药代动力学参数，HMS可能适用于预测人体受试者血浆中MT的浓度。当前研究可应用于使用水基载体经皮递送MT并制备MT剂型。
