Miyoshi M, Imoto T, Hiji Y
Department of Physiology, Faculty of Medicine, Tottori University, Yonago, Japan.
Reg Anesth Pain Med. 1998 Mar-Apr;23(2):176-81. doi: 10.1097/00115550-199823020-00011.
The use of sodium bicarbonate for alkalinization of local anesthetics to improve their efficacy has some disadvantages including decreased stability of the solutions. The present study was performed to evaluate usefulness of cyclodextrins (CDs) in improving the solubility and stability of local anesthetic solutions at near physiologic pH without precipitation.
Solubility of local anesthetics with or without CDs in physiologic saline was investigated by monitoring cloudiness or precipitate formation visually and by recording absorbance at 620 nm. Interaction of anesthetic and CD was also studied spectrophotometrically using spectral change of the drugs associated with the inclusion complex formation.
Cyclodextrins improved the solubility and stability of the four local anesthetics studied (dibucaine, tetracaine, bupivacaine, and lidocaine). In the neutral pH region, the effects of the CDs were more significant with dibucaine and tetracaine, which are more hydrophobic than the other two. A type of effective CD was different for each anesthetic depending partly on the tendency to form inclusion complex with local anesthetic. The local anesthetic solutions solubilized by CDs were found to remain clear for more than 72 hours without any visible precipitation or turbidity at neutral pHs.
The improved solubility of local anesthetics by adding CD may be caused by inclusion complex formation of CD with local anesthetics. This new preparation for the alkalinized water-soluble anesthetic solutions may be useful for practical application in the clinical setting, although this awaits further study.
使用碳酸氢钠碱化局部麻醉药以提高其疗效存在一些缺点，包括溶液稳定性降低。本研究旨在评估环糊精（CDs）在接近生理pH值时提高局部麻醉药溶液溶解度和稳定性且不产生沉淀的有效性。
通过肉眼观察浑浊或沉淀形成以及记录620nm处的吸光度，研究了含或不含CDs的局部麻醉药在生理盐水中的溶解度。还使用与包合物形成相关的药物光谱变化，通过分光光度法研究了麻醉药与CD的相互作用。
环糊精提高了所研究的四种局部麻醉药（丁卡因、丁哌卡因、布比卡因和利多卡因）的溶解度和稳定性。在中性pH区域，CDs对丁卡因和丁哌卡因的影响更为显著，这两种药物比其他两种更疏水。每种麻醉药的有效CD类型不同，部分取决于与局部麻醉药形成包合物的倾向。发现用CDs增溶的局部麻醉药溶液在中性pH值下可保持清澈超过72小时，无任何可见沉淀或浑浊。
添加CD提高局部麻醉药的溶解度可能是由于CD与局部麻醉药形成了包合物。这种用于碱化水溶性麻醉药溶液的新制剂可能在临床环境中具有实际应用价值，尽管这有待进一步研究。
