二水合羊角酸镁与胆钙化醇、甲萘醌-7协同联合治疗高血糖咀嚼片的研制、优化、表征及药代动力学研究。

IF 1.5 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Hitesh Verma, Rajeev Garg
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引用次数: 1

摘要

本研究的目的是根据ICH Q8 (R2)的产品开发指南,开发和优化含二水合角梨酸镁(MOD)、胆钙化醇(CHOL)和甲基萘醌-7 (MK-7)协同组合的咀嚼片。在风险评估后,采用30组试验设计(DoE)评价关键变量对咀嚼片质量属性的影响。优选出的最佳配方为:粘结剂14 mg/片、崩解剂31 mg/片、润滑剂11.377 mg/片,颗粒化时间为7.23 min。对制备的片剂进行处方药典和法规质量检查。优化后的配方在酸性介质(0.1 N HCl)中的崩解时间为6.06 min, 15 min内MOD的溶出率为87.39%,保证了配方在口服后呈溶液状。在加速条件下的稳定性研究表明,所开发的配方可以在整个保质期内保持其质量特征。咀嚼片在雄性Wistar大鼠体内的药代动力学研究表明,MOD达到最大血浆或血清浓度(Tmax)的时间为3 h, CHOL和MK-7达到最大血浆或血清浓度(Tmax)的时间为6 h。MOD、CHOL和MK-7的最大血浆或血清浓度(Cmax)分别为7.233±1.159、8.182±0.783和8.331±0.863 μg/mL [mean±standard deviation (SD)]。MOD、CHOL和MK-7的曲线下面积(AUC 0-t)分别为80.692±11.197、124.325±17.101和126.568±12.064 μg.mL.h-1 (mean±SD)。将咀嚼片的药代动力学数据与纯药混合后的药代动力学数据进行比较,证明所研制的配方能够有效地将三种营养物质全部输送到血液中,并能引起预期的药理反应。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Development, optimization and characterization of chewable tablet containing synergistic combination of magnesium orotate dihydrate with cholecalciferol and menaquinone-7 for management of hyperglycemia and its pharmacokinetic study.

The objective of the present research is to develop and optimize a chewable tablet containing synergistic combination of magnesium orotate dihydrate (MOD), cholecalciferol (CHOL) and menaquinone-7 (MK-7) as per product development guidelines of ICH Q8 (R2). The effects of critical variables on quality attributes of chewable tablets were evaluated using 30 runs based design of experiment (DoE) after risk assessment. Optimized formulation was found to be the one that was prepared with moderate granulation time of 7.23 min and contained 14 mg/tablet binder, 31 mg/tablet disintegrant and 11.377 mg/tablet lubricant. Prepared tablets were evaluated for prescribed pharmacopoeial and regulatory quality checks. Optimized formulation was found to have very low disintegration time of 6.06 min and 87.39% dissolution of MOD within 15 min in acidic media (0.1 N HCl), which ensure that the developed formulation behaves as a solution following oral administration. Stability studies under accelerated conditions revealed that the developed formulation can retain its quality characteristics throughout its shelf life. Pharmacokinetics study of chewable tablets in male Wistar rats shows that the time to reach maximum plasma or serum concentration (Tmax) was 3 h for MOD and 6 h for both CHOL and MK-7. Maximum plasma or serum concentration (Cmax) of MOD, CHOL and MK-7 was found to be 7.233 ± 1.159, 8.182 ± 0.783 and 8.331 ± 0.863 μg/mL [mean ± standard deviation (SD)], respectively. The area under the curve (AUC 0-t) for MOD, CHOL and MK-7 was 80.692 ± 11.197, 124.325 ± 17.101 and 126.568 ± 12.064 μg.mL.h-1 (mean ± SD), respectively. Comparison of pharmacokinetic data of chewable tablets with a mixture of pure drugs proves that the developed formulation can efficiently deliver all the three nutrients in blood and is capable to elicit desired pharmacological response.

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来源期刊
Magnesium research
Magnesium research 医学-内分泌学与代谢
CiteScore
3.50
自引率
9.40%
发文量
6
审稿时长
>12 weeks
期刊介绍: Magnesium Research, the official journal of the international Society for the Development of Research on Magnesium (SDRM), has been the benchmark journal on the use of magnesium in biomedicine for more than 30 years. This quarterly publication provides regular updates on multinational and multidisciplinary research into magnesium, bringing together original experimental and clinical articles, correspondence, Letters to the Editor, comments on latest news, general features, summaries of relevant articles from other journals, and reports and statements from national and international conferences and symposiums. Indexed in the leading medical databases, Magnesium Research is an essential journal for specialists and general practitioners, for basic and clinical researchers, for practising doctors and academics.
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