Department of Pharmaceutics, National organization for drug Control and Research (NODCAR), Giza, Egypt.
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
AAPS PharmSciTech. 2018 Aug;19(6):2519-2532. doi: 10.1208/s12249-018-1081-5. Epub 2018 Jun 12.
Diabetes mellitus is one of the leading causes of death due to the persistent hyperglycemia that leads to potential complications. Lack of patients' adherence to their prescribed medication regimens, due to the requirement of frequent dosing, leads to failure of 40-50% of patients to manage their disease. Thus, microsponges of the novel short half-life mitiglinide calcium (MTG) were formulated using Quasi-emulsion solvent diffusion method, employing Eudragit RS100, ethyl cellulose, and polyvinyl alcohol, then characterized in terms of production yield, entrapment efficiency, particle size, in vitro buoyancy, in vitro drug release, and in vivo pharmacokinetics in rabbits. Optimization was done using response surface methodology; the optimized formulation was investigated by FTIR, DSC, and SEM. Results revealed that the optimized MTG microsponge was successfully formulated with high production yield (61.61% ± 0.6), entrapment efficiency (77.7% ±1.37), and particle size of 192.76 μm and it remained buoyant over simulated gastric fluid for 24 h with high percentage of in vitro buoyancy (91.01% ± 2.5). Moreover, it sustained the in vitro drug release with cumulative % release of 83.74 ± 1.5 after 24 h. This microsponge was highly porous in nature with interconnected pores where MTG was entrapped with good compatibility as confirmed by SEM, DSC, and FTIR analysis; Pharmacokinetic studies showed improvement in C and AUC (1.92- and 20.68-fold, respectively) with marked prolongation in MRT and t (7.22- and 7.97-fold, respectively) than the marketed tablet. Thus, it is a promising approach to improve diabetic patients' compliance by eliminating the necessity of frequent dosing thus attaining better diabetes control.
糖尿病是导致死亡的主要原因之一，其持续性高血糖会导致潜在并发症。由于需要频繁给药，患者对规定药物治疗方案的依从性较差，导致 40-50%的患者无法控制疾病。因此，采用准乳液溶剂扩散法，使用 Eudragit RS100、乙基纤维素和聚乙烯醇，制备新型半衰期短的米格列奈钙（MTG）微海绵，并对其产率、包封效率、粒径、体外漂浮性、体外药物释放和在兔体内的药代动力学进行了表征。通过响应面法进行了优化；通过 FTIR、DSC 和 SEM 对优化的配方进行了研究。结果表明，成功制备了优化的 MTG 微海绵，具有较高的产率（61.61%±0.6）、包封效率（77.7%±1.37）和粒径为 192.76 μm，在模拟胃液中能保持 24 h 的漂浮性，体外漂浮率高（91.01%±2.5）。此外，它能持续释放药物，24 h 后的累积释放率为 83.74%±1.5%。这种微海绵具有高度多孔的性质，其中含有相互连接的孔隙，MTG 被包封在其中，具有良好的相容性，这一点通过 SEM、DSC 和 FTIR 分析得到了证实；药代动力学研究表明，与市售片剂相比，C 和 AUC 分别提高了 1.92-和 20.68 倍，MRT 和 t 分别延长了 7.22-和 7.97 倍，这表明该方法有望通过消除频繁给药的必要性来提高糖尿病患者的依从性，从而更好地控制糖尿病。
