Effect of cyclodextrins on the complexation and transdermal delivery of bupranolol through rat skin
Effect of cyclodextrins on the complexation and transdermal delivery of bupranolol through rat skin
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DOI：
10.1016/j.ijpharm.2003.11.004
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发表时间：
2004-03-01
影响因子：
5.8
通讯作者：
Pandit, JK
中科院分区：
文献类型：
--
作者：
Babu, RJ;Pandit, JK
布萘洛尔（BPL）是一种有效的β-受体阻滞剂，其广泛的首过代谢（>90%）和快速的消除半衰期（1.5-2.0 h）使其非常适合开发为经皮给药系统（TDS）。羟丙基β CD（HP β CD）和部分甲基化PCD（PM β CD）用作BPL的渗透促进剂。通过相溶解度、X射线衍射和差示扫描量热法（DSC）对BPL与这些环糊精（CD）形成的包合物进行了表征。采用并行扩散池和pH7.4的磷酸盐缓冲液（PBS）研究了CD对BPL经皮渗透的促进作用。CD以不同浓度与0.4%（w/v）BPL以及过量的BPL（1.0%，w/v）一起使用，CD不能络合所有的BPL，并且药物呈水性悬浮液的形式。当使用低浓度CD（HP β CD和PM β CD分别高达2%和5% w/v浓度）时，BPL从其水悬浮液（0.4%，w/v）中的渗透显着增加（P < 0.01）。在较高的CD浓度下，BPL的渗透降低;并且10%（w/w）的两种CD显示与对照相似的通量值（无增强剂，P > 0.05）。对于HP β CD和PM β CD，BPL从其1.0%（w/v）水悬浮液中的渗透随着CD浓度的增加而增加，直至10%（w/v）。在10%（w/v）浓度的HP β CD和PM β CD下，来自其1.0%水悬浮液的BPL通量分别增加3.8倍和4.6倍（P < 0.01和P < 0.001）。用CD预处理皮肤的渗透数据表明HP β CD对皮肤没有影响，而PM β CD显著降低了BPL的皮肤屏障，如通过PM β CD预处理使通量增加1.7倍所示（P < 0.001）。总体而言，发现HP β CD和PM β CD都适合于改善BPL的溶解度和渗透增强。(C)2003 Elsevier B. V.保留所有权利。
Bupranolol (BPL) is a potent beta-blocking agent, the extensive first-pass metabolism (>90%) and rapid elimination half-life (1.5-2.0 h) of this drug make it well suited to be developed as a transdermal delivery system (TDS). Hydroxypropyl betaCD (HPbetaCD) and partially methylated PCD (PMbetaCD) were used as penetration enhancers for BPL. The formation of inclusion complex of BPL with these cyclodextrins (CDs) was characterized in solution and solid states by phase solubility, X-ray diffractometry and differential scanning calorimetry (DSC) analyses. The effect of CDs on the permeation enhancement of BPL through rat skin was studied using side-by-side diffusion cells and pH 7.4 phosphate-buffered saline (PBS). CDs were employed at different concentrations with 0.4% (w/v) BPL as well as with excess quantity of BPL (1.0%, w/v) that CDs could not complex all the BPL and the drug was in the form of an aqueous suspension. The permeation of BPL from its aqueous suspension (0.4%, w/v) significantly increased when CDs were used at low concentrations (up to 2 and 5%, w/v concentration for HPbetaCD and PMbetaCD, respectively) (P < 0.01). At higher CD concentrations, the permeation of BPL decreased; and both CDs at 10% (w/w), showed similar flux values to that of control (no enhancer, P > 0.05). The permeation of BPL from its 1.0% (w/v) aqueous suspension increased with increase in concentration of CD up to 10% (w/v) for HPbetaCD and PMbetaCD. At 10% (w/v) concentration of HPbetaCD and PMbetaCD, the flux of BPL from its 1.0% aqueous suspension increased 3.8- and 4.6-fold (P < 0.01 and P < 0.001, respectively). The permeation data of skin pretreatment with CDs indicate that HPbetaCD had no effect on the skin, whereas PMbetaCD significantly reduced the skin barrier for BPL, as shown by 1.7-fold increase in the flux by PMbetaCD pretreatment (P < 0.001). Overall, both HPbetaCD and PMbetaCD were found to be suitable for improving the solubility and penetration enhancement of BPL. (C) 2003 Elsevier B.V. All rights reserved.