{"title":"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。","authors":"Hitesh Verma, Rajeev Garg","doi":"10.1684/mrh.2021.0487","DOIUrl":null,"url":null,"abstract":"<p><p>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 (T<sub>max</sub>) was 3 h for MOD and 6 h for both CHOL and MK-7. Maximum plasma or serum concentration (C<sub>max</sub>) 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 <sub>0</sub>-<sub>t</sub>) for MOD, CHOL and MK-7 was 80.692 ± 11.197, 124.325 ± 17.101 and 126.568 ± 12.064 μg.mL.h<sup>-1</sup> (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.</p>","PeriodicalId":18159,"journal":{"name":"Magnesium research","volume":null,"pages":null},"PeriodicalIF":1.5000,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":"{\"title\":\"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.\",\"authors\":\"Hitesh Verma, Rajeev Garg\",\"doi\":\"10.1684/mrh.2021.0487\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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 (T<sub>max</sub>) was 3 h for MOD and 6 h for both CHOL and MK-7. Maximum plasma or serum concentration (C<sub>max</sub>) 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 <sub>0</sub>-<sub>t</sub>) for MOD, CHOL and MK-7 was 80.692 ± 11.197, 124.325 ± 17.101 and 126.568 ± 12.064 μg.mL.h<sup>-1</sup> (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.</p>\",\"PeriodicalId\":18159,\"journal\":{\"name\":\"Magnesium research\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.5000,\"publicationDate\":\"2021-05-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Magnesium research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1684/mrh.2021.0487\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Magnesium research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1684/mrh.2021.0487","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
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.
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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