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琥珀酸舒马曲坦压制包衣漂浮脉冲式给药系统的研制与优化

Development and optimization of press coated floating pulsatile drug delivery of sumatriptan succinate.

作者信息

Jagdale Swati C, Pawar Chandrakala R

机构信息

Department of Pharmaceutics, MAEER's Maharashtra Institute of Pharmacy, MIT Campus, S.No124, Kothrud, Pune- 411 038, Maharashtra, India.

出版信息

Curr Drug Deliv. 2014;11(3):392-400. doi: 10.2174/156720181103140530150823.

Abstract

Floating pulsatile is combined approach designed according to circadian rhythm to deliver the drug at right time, in right quantity and at right site as per pathophysiological need of disease with prolong gastric residence and lag phase followed by burst release. As the migraine follows circadian rhythm in which headache is more painful at the awakening time, the dosage form should be given during night time to release drug when pain get worsen. Present work deals with formulation and optimization of floating pulsatile tablet of sumatriptan succinate. Core tablet containing crospovidone as superdisintegrant (10%) showed burst release. Lag time was maintained using swellable polymer as polyoxN12K and xanthum gum. 3(2) experimental design was carried out. Developed formulations were evaluated for physical characteristics, in vitro and in vivo study. Optimized batch F2 with concentration of polyox N12K (73.43%) and xanthum gum (26.56%) of total polymer weight showed floating lag time 15±2 sec, drug content 99.58±0.2 %, hardness 6±0.2 Kg/cm(2) and drug release 99.54±2% with pulsatile manner followed lag period of 7±0.1h. In vivo x-ray study confirms prolong gastric residence of system. Programmable pulsatile release has been achieved by formulation F2 which meet demand of chronotherapeutic objective of migraine.

摘要

漂浮脉冲制剂是一种根据昼夜节律设计的联合给药方法,可根据疾病的病理生理需求,在合适的时间、以合适的剂量、在合适的部位给药,延长药物在胃内的滞留时间和滞后阶段,随后实现突释。由于偏头痛遵循昼夜节律,在醒来时头痛更为剧烈,因此应在夜间给药,以便在疼痛加剧时释放药物。目前的工作涉及琥珀酸舒马曲坦漂浮脉冲片的制剂研发和优化。含有交联聚维酮作为超级崩解剂(10%)的核心片显示出突释效果。使用可膨胀聚合物如聚氧乙烯N12K和黄原胶来维持滞后时间。进行了3(2)实验设计。对研发的制剂进行了物理特性、体外和体内研究评估。优化后的批次F2中,聚氧乙烯N12K的浓度为聚合物总重量的73.43%,黄原胶的浓度为26.56%,其漂浮滞后时间为15±2秒,药物含量为99.58±0.2%,硬度为6±0.2 Kg/cm²,药物释放率为99.54±2%,呈脉冲式释放,滞后时间为7±0.1小时。体内X射线研究证实了该系统在胃内的滞留时间延长。制剂F2实现了可编程的脉冲释放,满足了偏头痛时辰治疗的目标需求。

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