设计和优化用于消化性溃疡愈合的泮托拉唑钠粘液水凝胶微胶囊

Rashad M. Kaoud, Mustafa Hasan Alwan, Mohammed Amran, Hayder Adnan Fawzi
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摘要

水凝胶作为一种胃肠道给药技术备受关注。本研究旨在设计一种口服粘液粘附缓释剂型,以降低消化性溃疡并发症(PUC)。研究采用方框-贝肯统计设计法,将泮托拉唑钠(PZS)加入水凝胶微胶囊(HGMC)中,开发出制备方法。通过离子凝胶技术将 PZS 加入 HGMC,以海藻酸钠作为胶凝剂,氯化钙作为交联剂,壳聚糖作为缓释剂。优化后的 PZS-HGMC 配方直径为 2.506 毫米,膨胀率为 838.2%,封装效率为 93.8%。扫描电子显微镜图像显示微胶囊呈球形。在模拟胃液中浸泡两小时后,PZS从HGMC中的体外释放率为13.2%1±0.08%,而纯PZS在相同条件下的表观溶解度为95.24%±3.2%。24 小时后,优化配方释放的 PZS 百分比为 69.84±2.4%,这表明其具有持续释放模式。体内研究结果表明,与标准 PZS疗法相比,使用 PZS-HGMC 配方治疗大鼠诱发溃疡的愈合情况有所改善;因此,获得的粘液粘附性 HGMC 被认为是 PUC 治疗的一种潜在给药策略。
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Design and optimization of pantoprazole sodium mucoadhesive hydrogel microcapsules for the healing of peptic ulcers
Hydrogels have gained much focus as a gastro-retentive technology for drug delivery. The current study aimed to design an oral mucoadhesive sustained-release dosage form to lower peptic ulcer complications (PUC). Using the Box-Behnken statistical design, the preparation method was developed by incorporating pantoprazole sodium (PZS) into hydrogel microcapsules (HGMC). The PZS was incorporated into the HGMC via an ion gelation technique, with sodium alginate as the gelling agent, calcium chloride as the crosslinking agent, and chitosan as the agent for sustained release. The optimized formulation of PZS-HGMC showed a diameter of 2.506 mm, a swelling rate of 838.2%, and an encapsulation efficiency of 93.8%. Scanning electron microscopy images revealed the microcapsules’ spherical shape. The in vitro release of the PZS from the HGMC after two hours in a simulated gastric fluid was 13.2%1±0.08%, compared with the apparent solubility of the pure PZS under the same conditions (95.24%±3.2%). After 24 hours, the percent of PZS released from the optimized formula was 69.84±2.4%, which indicates a sustained release pattern. The results from the in vivo study demonstrated improved healing of the induced ulcers in rats when treated with the PZS-HGMC formulation as compared to the standard PZS therapy; therefore, the obtained mucoadhesive HGMC was considered a potential drug delivery strategy for PUC therapy.
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