盐酸左布比卡因原位凝胶注射剂的制备及其在动物体内的药代动力学和药效学

采用磷脂为基质的新型原位凝胶作为盐酸左布比卡因缓释注射剂的载体。通过筛选磷脂类型、磷脂/乙醇比例、水分比例确定稳定载药的处方。制备的处方进行了初步表征，符合原位凝胶的特点。进行了比格犬药代动力学考察，上述处方的tmax滞后，t1/2延长，缓释特征明显。在豚鼠中进行了药效学评价，上述处方局部麻醉效果显著，相对于市售注射液，可维持长达48~72 h的局麻效果。该新型原位凝胶具备良好的开发潜力。
The purpose of this study was to develop a novel phospholipidas-based in-situ gel sustained-release formulation of levobupivacaine hydrochloride injection. Appropriate formulation was screened based on the factors such as phospholipid type, ratio of phospholipid to ethanol, ratio of water to phospholipid-ethanol mixture, which indicated typical in-situ gel profiles. Pharmacokinetic study using beagles showed that there were delayed tmax and prolonged t1/2 in levobupivacaine plasma-time profile after administration of the phospholipidas-based in-situ gel formulation if compared to commercially available conventional levobupivacaine hydrochloride injection. Pharmacodynamic studies conducted on guinea-pig demonstrated that it maintained 48-72 hr regional anesthesia, much longer than that of the anesthesia in the group receiving conventional injection. Hence, this novel in-situ gel intended for injection is worthy of development