Institute of Pharmaceutical Education and Research (IPER), Borgaon (Meghe) Wardha, Maharashtra, India.
J Drug Target. 2010 Apr;18(3):223-34. doi: 10.3109/10611860903386938.
Mucoadhesive temperature-mediated in situ gel formulations using chitosan and hydroxyl propyl methyl cellulose were used to enhance intranasal (i.n.) delivery of the dopamine D2 agonist ropinirole to the brain. Formulations were tested for gelation time, thermosensitivity, mucoadhesion, in vitro release and permeation, in vitro cytotoxicity, nasal clearance, in vivo bioavailability and brain uptake. In vivo bioavailability and brain uptake of ropinirole were assessed in albino rats following intranasal administration of 99mTc-ropinirole in situ gel, intranasal ropinirole solution and intravenous (i.v.) ropinirole solution. Radiolabeled ropinirole uptake was calculated as a fraction of administered dose. The absolute bioavailabilty of ropinirole from the temperature-mediated in situ gelling nasal formulation was 82%. The AUC (0-480 min) in brain after nasal administration of ropinirole in situ gel was 8.5 times (869 +/- 250% x min/g versus 102 +/- 20% x min/g) that obtained following i.v. administration, this value was also considerably higher (869 +/- 250% x min/g versus 281 +/- 52% x min/g) than that achieved with intranasal ropinirole solution. High brain direct drug transport percentage (DTP; 90.36%) and drug targeting index (DTI) > 1 confirms direct nose to brain transport of the intranasal in situ gel formulation of ropinirole.
使用壳聚糖和羟丙基甲基纤维素的粘膜粘附温度介导的原位凝胶制剂被用于增强多巴胺 D2 激动剂罗匹尼罗向大脑的鼻内（i.n.）传递。对制剂的胶凝时间、热敏性、粘膜粘附性、体外释放和渗透、体外细胞毒性、鼻清除率、体内生物利用度和脑摄取进行了测试。在经鼻给予 99mTc-罗匹尼罗原位凝胶、经鼻罗匹尼罗溶液和静脉（i.v.）罗匹尼罗溶液后，在白化大鼠中评估了罗匹尼罗的体内生物利用度和脑摄取。放射性标记的罗匹尼罗摄取被计算为给予剂量的分数。温度介导的原位凝胶鼻腔制剂的罗匹尼罗绝对生物利用度为 82%。经鼻给予罗匹尼罗原位凝胶后，脑内的 AUC（0-480 分钟）是静脉给予后的 8.5 倍（869 +/- 250% x min/g 与 102 +/- 20% x min/g），这一值也明显高于经鼻给予罗匹尼罗溶液时的（869 +/- 250% x min/g 与 281 +/- 52% x min/g）。高脑直接药物转运百分比（DTP；90.36%）和药物靶向指数（DTI）>1 证实了罗匹尼罗经鼻原位凝胶制剂的直接鼻脑转运。
