Ravi P R, Aditya N, Patil S, Cherian L
a Pharmacy Department , BITS-Pilani Hyderabad Campus , Jawaharnagar , Andhra Pradesh , India.
Drug Deliv. 2015;22(7):903-10. doi: 10.3109/10717544.2013.860501. Epub 2013 Nov 29.
Intranasal thermosensitive gel for rasagiline mesylate (RM) was developed for effective treatment of Parkinson's disease. Intranasal gels were prepared by combination of poloxamer 407 and poloxamer 188 (1:1) with mucoadhesive polymers (carbopol 934 P and chitosan). The formulations were evaluated for sol-gel transition temperature, in-vitro drug release and in-vivo mucociliary transit time. Further, optimal intranasal gel formulations were tested for in-vivo pharmacokinetic behavior, nasal toxicity studies and brain uptake studies. It was found that optimal formulations had acceptable gelation temperature (28-33 °C) and adequate in-vitro drug release profile. Pharmacokinetic study in rabbits showed significant (p < 0.05) improvement in bioavailability (four- to six-folds) of the drug from intranasal gels than oral solution. Chronic exposure studies in Wistar rats showed that these intranasal gels were non-irritant and non-toxic to rat nasal mucosa. Estimation of RM in rat brain tissue showed significant (p < 0.01) improvement in uptake of RM form intranasal gel formulations than nasal solution.
开发了用于甲磺酸雷沙吉兰（RM）的鼻内热敏凝胶，以有效治疗帕金森病。通过泊洛沙姆407和泊洛沙姆188（1:1）与粘膜粘附聚合物（卡波姆934P和壳聚糖）组合制备鼻内凝胶。对制剂进行了溶胶-凝胶转变温度、体外药物释放和体内粘膜纤毛转运时间的评估。此外，对最佳鼻内凝胶制剂进行了体内药代动力学行为、鼻毒性研究和脑摄取研究。结果发现，最佳制剂具有可接受的胶凝温度（28-33°C）和足够的体外药物释放曲线。兔体内药代动力学研究表明，与口服溶液相比，鼻内凝胶给药后药物的生物利用度显著提高（4至6倍，p<0.05）。对Wistar大鼠的慢性暴露研究表明，这些鼻内凝胶对大鼠鼻粘膜无刺激性且无毒。大鼠脑组织中RM的测定表明，与鼻溶液相比，鼻内凝胶制剂中RM的摄取显著提高（p<0.01）。
