用于双相给药格列吡嗪的胶囊中胶囊技术的制备与评估

Rupali Rathod, Manoj Bari, Shaikh Samir
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摘要

在本研究工作中,对用于格列吡嗪双相给药的胶囊中胶囊技术进行了配制和评估。该研究结合了快速释放液体填充胶囊和缓释珠粒填充胶囊的优点,以满足双相给药系统的优化要求。使用海藻酸钠、果胶等天然聚合物,通过离子营养凝胶法制备格列吡嗪缓释珠,并将其填充到较小的胶囊中。使用蓖麻油载体制备格列吡嗪速释液体分散体,并进一步制备格列吡嗪乳剂。将这种快释液体和缓释微珠填充胶囊进一步装入较大的胶囊体中,并用水醇溶液密封胶囊。对不同批次的制剂进行了理化研究、包埋效率、药物含量、体外药物释放和稳定性研究。相互作用研究表明,本研究中使用的药物和聚合物之间不存在相互作用。优化后的胶囊中胶囊配方在 30 分钟内释放了 22.65±0.74% 的药物,在 12 小时内释放了 95.04±0.88% 的药物。格列吡嗪胶囊剂的药物释放曲线非常符合 Pepas 模型,其次是零阶、一阶和 Korsmeyer-peppa 模型。Korsmeyer-Peppas 模型分析表明,药物的释放遵循非费克转运机制。稳定性结果表明,在 45°C/75%RH 条件下贮藏 4 个月,优化配方的各项参数均不受影响。胶囊中胶囊给药的目标是使装载剂量达到血浆中的治疗药物水平,以加快起效速度,而维持剂量则能长期保持有效的治疗水平。制备的格列吡嗪双相胶囊帽将用于治疗糖尿病。
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Formulation and Evaluation of Capsule-in-Capsule Technology for Biphasic delivery of Glipizide
In the present research work, to formulation and evaluation of capsule-in-capsule technology for biphasic delivery of Glipizide. The advantages of fast releasing liquid-filled-capsules and slow release beads-filled-capsules were combined to meet the optimized requirements of our biphasic drug delivery system. Glipizide slow releasing beads were prepared by ionotrophic gelation method by using natural polymers like Sodium alginate, Pectin and were filled into a smaller capsule. Glipizide fast releasing liquid dispersion was prepared by using either Castor oil carriers and further prepared a glipizide emulsion. This fast releasing liquid and slow releasing beads-filled-capsule was further inserted into a bigger capsule body and Seal the capsule by hydro alcoholic solution. The various formulation batches were subjected to physicochemical studies, entrapment efficiency, drug content, in vitro drug release and stability studies. Interaction studies reveal that there was no interaction between drug and polymers employed in this study. The optimized capsule-in-a-capsule formulation released 22.65±0.74% of drug at the end of 30 min and 95.04±0.88% of drug at the end of 12h. The drug release profile of Glipizide capsule-in-a-capsule formulation fits well with Pepas model followed by zero order, first order and Korsemeyer-peppa’s model. Korsmeyer-Peppas model analysis indicated that the drug release followed non-Fickian transport mechanism. The stability results indicate that the various parameters of our optimized formulation are not affected on storage at 45°C/75%RH up to 4 months. Target of capsule-in-capsule drug delivery loading dose reaches therapeutic drug level in blood plasma for quicker onset of action and Maintenance dose which maintain an effective therapeutic level for prolong period. The prepared Glipizide biphasic cap-in-cap will be used for treatment of Diabetes.
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