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载有双氯芬酸的自组装器官凝胶用于局部强化疼痛和炎症治疗的体外与体内相关性研究。

Self-assembling Organogels Loaded with Tenoxicam for Local Intensive Pain and Inflammation Cure: In Vitro and In Vivo Correlation.

机构信息

Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Al-Azhar University, Assiut, 71524, Egypt.

Department of Pharmaceutical Technology, Faculty of Pharmacy, Minofia University, Minofia, Egypt.

出版信息

AAPS PharmSciTech. 2024 Jan 23;25(1):18. doi: 10.1208/s12249-024-02742-9.

Abstract

Due to tenoxicam (TX)'s poor aqueous solubility (0.072 mg/ml), it is poorly absorbable in the GIT, and the long-term oral administration of TX may cause severe GIT disturbances. Topical administration of TX can help in bypassing the GIT adverse effects. Therefore, in the present work, we constructed different pluronic/lecithin organogels (PLOs) for topical delivery of TX. PLO was constructed simply via direct mixing of an aqueous pluronic solution with lecithin solution. The prepared PLO formulations were characterized for their physicochemical properties including pH, drug content, visual inspection, viscosity, and spreadability. Also, the in vitro release and kinetic studies were carried out to investigate the mechanism of drug release. Moreover, the in vivo studies were carried out by investigating the anti-inflammatory and analgesic activities using albino male rats. The results showed that the modified PLOs have good physicochemical properties. The viscosity of the modified gels is a direct proportionality with both lecithin and pluronic concentrations. Also, subsequently, the drug release rate is directly proportional to gel viscosity. Moreover, the in vivo studies showed that the modified PLOs (F19) showed a significant ( < 0.05%) paw edema inhibition and pain analgesia compared with other investigated groups. Also, the results indicated that the increase in dose is accompanied by higher activity and a longer duration of action which extended to 12 h. Hence, the modified PLOs are promising safe candidates or vehicles for effective TX loading with sustained delivery behavior.

摘要

由于替诺昔康(TX)的水溶性差(0.072mg/ml),在胃肠道中吸收不良,长期口服 TX 可能会引起严重的胃肠道紊乱。TX 的局部给药可以帮助绕过胃肠道不良反应。因此,在本工作中,我们构建了不同的泊洛沙姆/卵磷脂有机凝胶(PLO)用于 TX 的局部递药。PLO 通过将水性泊洛沙姆溶液与卵磷脂溶液直接混合简单构建。对所制备的 PLO 制剂进行了理化性质的表征,包括 pH 值、药物含量、目视检查、粘度和铺展性。还进行了体外释放和动力学研究,以研究药物释放的机制。此外,通过研究白化雄性大鼠的抗炎和镇痛活性进行了体内研究。结果表明,改性 PLO 具有良好的理化性质。改性凝胶的粘度与卵磷脂和泊洛沙姆的浓度呈直接比例关系。此外,随后,药物释放速率与凝胶粘度成正比。此外,体内研究表明,与其他研究组相比,改性 PLO(F19)表现出显著的(<0.05%)爪子水肿抑制和疼痛镇痛作用。此外,结果表明,剂量增加伴随着更高的活性和更长的作用持续时间,最长可达 12 小时。因此,改性 PLO 是有前途的安全候选物或载体,可有效负载替诺昔康并具有持续释放行为。

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