设计专家软件辅助开发和评估具有改善的体内抗糖尿病活性的恩格列净和西格列汀复方片剂。

Design expert software assisted development and evaluation of empagliflozin and sitagliptin combination tablet with improved in-vivo anti-diabetic activities.

作者信息

Hossain Md Saddam, Jahan Sadia, Al Rezwan Rahman Sad, Rahman Mashiur, Kumar Diponkor, Paul Susmita, Chandra Rajbangshi Joy

机构信息

Department of Pharmacy, Faculty of Science, Comilla University, Bangladesh.

Bangladesh Reference Institute for Chemical Measurements, Dhaka, Bangladesh.

出版信息

Heliyon. 2023 Mar 4;9(3):e14259. doi: 10.1016/j.heliyon.2023.e14259. eCollection 2023 Mar.

DOI:10.1016/j.heliyon.2023.e14259

PMID:36938401

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10015239/

Abstract

BACKGROUND

The combination of empagliflozin and sitagliptin to treat type-2 diabetes might be more economical and patient compliance with an additive improvement in glycemic control due to complementary modes of action.

AIM OF THE STUDY

To design, formulate and optimize an immediate tablet dosage form containing empagliflozin and sitagliptin utilizing statistically reliable study design followed by in-vitro and in-vivo testing.

METHOD

ology: To determine the effects of copovidone (X1) and croscarmellose sodium (X2) amounts on the dependent variables of disintegration time and percent drug release, the formulation was developed using Design Expert Software v.13's direct compression method-based central composite design optimization study. The formulations' assay, dissolution, friability, hardness, weight variation, disintegration, and anti-diabetic effects were evaluated in comparison to the standard drug. The analysis included the use of high performance liquid chromatography (HPLC) assay methods. Mice were employed to investigate the efficacy of an anti-diabetic drug after they were administered a high-fat diet and two injections of streptozotocin at a dosage of 30 mg/kg BW each.

RESULTS

Formulation of F3 out of nine had all in-vitro parameters at the most satisfactory condition. It was found that assay of the best formulation is 100.99% and 100.19% for empagliflozin and sitagliptin respectively. The disintegration time of F3 was found at 5.32 min. Percentage release of empagliflozin in 30 min was found 89.05% while sitagliptin was with 93.76%. The results showed that administration of F3 significantly reduced FBG (68.61%, p < 0.0001), total cholesterol levels (70.29 ± 0.48; p < 0.0001), triglycerides (70.20 ± 0.40, p < 0.0001); HDL levels (52.50 ± 0.31; p < 0.0001), LDL levels (33.34 ± 0.28; p < 0.0001), compared to diabetic control, this effect was comparable to metformin treatment.

CONCLUSION

The direct compression approach has been used to develop, and optimize a new combination tablet incorporating empagliflozin and sitagliptin with better dissolution rate and anti-diabetic action.

摘要

背景

恩格列净和西格列汀联合治疗2型糖尿病可能更具经济性，且由于作用方式互补，在血糖控制方面有累加改善作用，患者依从性更好。

研究目的

采用统计学可靠的研究设计，随后进行体外和体内测试，设计、制备并优化一种含有恩格列净和西格列汀的速释片剂剂型。

方法

为了确定共聚维酮（X1）和交联羧甲基纤维素钠（X2）用量对崩解时间和药物释放百分比等因变量的影响，使用Design Expert Software v.13基于直接压片法的中心复合设计优化研究来开发制剂。与标准药物相比，评估了制剂的含量测定、溶出度、脆碎度、硬度、重量差异、崩解度和抗糖尿病作用。分析包括使用高效液相色谱（HPLC）含量测定方法。给小鼠喂食高脂饮食并两次注射链脲佐菌素，剂量均为30 mg/kg体重，以研究抗糖尿病药物的疗效。

结果

九种制剂中的F3制剂所有体外参数均处于最满意状态。发现最佳制剂中恩格列净和西格列汀的含量测定分别为100.99%和100.19%。F3的崩解时间为5.32分钟。30分钟时恩格列净的释放百分比为89.05%，而西格列汀为93.76%。结果表明，与糖尿病对照组相比，给予F3可显著降低空腹血糖（68.61%，p < 0.0001）、总胆固醇水平（70.29±0.48；p < 0.0001）、甘油三酯（70.20±0.40，p < 0.0001）；高密度脂蛋白水平（52.50±0.31；p < 0.0001），低密度脂蛋白水平（33.34±0.28；p < 0.0001），这种效果与二甲双胍治疗相当。