Pontani R B, Misra A L
Pharmacol Biochem Behav. 1983 Mar;18(3):471-4. doi: 10.1016/0091-3057(83)90472-0.
A subcutaneously implantable buprenorphine delivery system utilizing cholesterol-glyceryltristearate matrix for prolonged release of drug is described. Implantable cylindrical pellets of buprenorphine (cholesterol 36 mg, glyceryltristearate 4 mg, buprenorphine hydrochloride 10 mg), diameter 3 mm, length 6 mm blocked the antinociceptive action (hot plate, 55 degrees C) of 10 mg kg-1 SC challenge dose of morphine in rats for 12 weeks or more (longer periods not evaluated). The cumulative percent release of buprenorphine from the test devices 2, 4, 6, 10 and 12 weeks after implantation was 27.4, 35.9, 37.6, 39.9 and 43.1, respectively. The release of buprenorphine from 10 mg pellets approximated first-order kinetics with half-lives of 0.85 and 50.24 weeks, for alpha and beta phases, respectively. The test devices possess the desirable characteristics of simplicity, biocompatibility, nontoxicity, ease of sterilization with ethylene oxide, small size for ease of insertion and removal, minimal encapsulation by surrounding tissue and an extended period of drug release unaffected by body metabolism. No side effects were seen in implanted rats which fed well and gained weight during entire treatment. Neither deterioration of implant nor any gross anatomic changes at implant site were apparent 12 weeks after pellet implantation.
描述了一种皮下可植入的丁丙诺啡给药系统，其利用胆固醇-三硬脂酸甘油酯基质实现药物的长效释放。可植入的丁丙诺啡圆柱形微丸（胆固醇36毫克、三硬脂酸甘油酯4毫克、盐酸丁丙诺啡10毫克），直径3毫米，长度6毫米，可在12周或更长时间（未评估更长时间）内阻断10毫克/千克皮下注射挑战剂量吗啡对大鼠的抗伤害感受作用（热板法，55摄氏度）。植入后2、4、6、10和12周，测试装置中丁丙诺啡的累积释放百分比分别为27.4%、35.9%、37.6%、39.9%和43.1%。10毫克微丸中丁丙诺啡的释放近似一级动力学，α相和β相的半衰期分别为0.85周和50.24周。该测试装置具有简单、生物相容性好、无毒、易于用环氧乙烷灭菌、尺寸小便于插入和取出、周围组织包封极少以及药物释放期延长不受身体代谢影响等理想特性。植入大鼠在整个治疗过程中进食良好且体重增加，未观察到副作用。微丸植入12周后，植入物未出现降解，植入部位也未出现明显的大体解剖学变化。
