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An Industrial Procedure for Pharmacodynamic Improvement of Metformin HCl via Granulation with Its Paracellular Pathway Enhancer Using Factorial Experimental Design

BACKGROUND: Sorbitan monostearate is a surfactant used in the food industry. It was proved as a penetration enhancer to metformin HCl via a paracellular pathway. It is solid at room temperature and has a low melting point. Therefore, it was selected, as a granulating agent for metformin HCl. METHODS...

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Autores principales: Mady, Omar Y, Al-Shoubki, Adam A, Donia, Ahmed A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8576103/
https://www.ncbi.nlm.nih.gov/pubmed/34764634
http://dx.doi.org/10.2147/DDDT.S328262
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author Mady, Omar Y
Al-Shoubki, Adam A
Donia, Ahmed A
author_facet Mady, Omar Y
Al-Shoubki, Adam A
Donia, Ahmed A
author_sort Mady, Omar Y
collection PubMed
description BACKGROUND: Sorbitan monostearate is a surfactant used in the food industry. It was proved as a penetration enhancer to metformin HCl via a paracellular pathway. It is solid at room temperature and has a low melting point. Therefore, it was selected, as a granulating agent for metformin HCl. METHODS: Multi-level factorial design was applied to determine the optimized formula for industrial processing. The selected formulations were scanned using an electron microscope. Differential scanning calorimetry was used to ascertain the crystalline state of a drug. A modified non-everted sac technique, suggested by the authors, was used to evaluate the in vitro permeation enhancement of the drug. To simulate the emulsification effect of the bile salt, a tween 80 was added to the perfusion solution. As a pharmacodynamic marker, blood glucose levels were measured in diabetic rats. RESULTS: The results showed that drug permeability increases in the presence of tween 80. Drug permeability from granules increased than that of the pure drug or pure drug with tween 80. The prepared granules decreased blood glucose levels of diabetic rats than the pure drug and drug plus tween 80. There was an excellent correlation between the results of the drug permeation percent in vitro and the dropping of blood glucose level percent in vivo. CONCLUSION: Improving the drug permeation and consequently, the drug pharmacodynamic effect in addition to an excellent micromeritics property of the prepared drug granules showed the dual enhancement effect of the suggested industrial procedure. Therefore, we suggest the same industrial procedure for other class III drugs.
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spelling pubmed-85761032021-11-10 An Industrial Procedure for Pharmacodynamic Improvement of Metformin HCl via Granulation with Its Paracellular Pathway Enhancer Using Factorial Experimental Design Mady, Omar Y Al-Shoubki, Adam A Donia, Ahmed A Drug Des Devel Ther Original Research BACKGROUND: Sorbitan monostearate is a surfactant used in the food industry. It was proved as a penetration enhancer to metformin HCl via a paracellular pathway. It is solid at room temperature and has a low melting point. Therefore, it was selected, as a granulating agent for metformin HCl. METHODS: Multi-level factorial design was applied to determine the optimized formula for industrial processing. The selected formulations were scanned using an electron microscope. Differential scanning calorimetry was used to ascertain the crystalline state of a drug. A modified non-everted sac technique, suggested by the authors, was used to evaluate the in vitro permeation enhancement of the drug. To simulate the emulsification effect of the bile salt, a tween 80 was added to the perfusion solution. As a pharmacodynamic marker, blood glucose levels were measured in diabetic rats. RESULTS: The results showed that drug permeability increases in the presence of tween 80. Drug permeability from granules increased than that of the pure drug or pure drug with tween 80. The prepared granules decreased blood glucose levels of diabetic rats than the pure drug and drug plus tween 80. There was an excellent correlation between the results of the drug permeation percent in vitro and the dropping of blood glucose level percent in vivo. CONCLUSION: Improving the drug permeation and consequently, the drug pharmacodynamic effect in addition to an excellent micromeritics property of the prepared drug granules showed the dual enhancement effect of the suggested industrial procedure. Therefore, we suggest the same industrial procedure for other class III drugs. Dove 2021-11-02 /pmc/articles/PMC8576103/ /pubmed/34764634 http://dx.doi.org/10.2147/DDDT.S328262 Text en © 2021 Mady et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Mady, Omar Y
Al-Shoubki, Adam A
Donia, Ahmed A
An Industrial Procedure for Pharmacodynamic Improvement of Metformin HCl via Granulation with Its Paracellular Pathway Enhancer Using Factorial Experimental Design
title An Industrial Procedure for Pharmacodynamic Improvement of Metformin HCl via Granulation with Its Paracellular Pathway Enhancer Using Factorial Experimental Design
title_full An Industrial Procedure for Pharmacodynamic Improvement of Metformin HCl via Granulation with Its Paracellular Pathway Enhancer Using Factorial Experimental Design
title_fullStr An Industrial Procedure for Pharmacodynamic Improvement of Metformin HCl via Granulation with Its Paracellular Pathway Enhancer Using Factorial Experimental Design
title_full_unstemmed An Industrial Procedure for Pharmacodynamic Improvement of Metformin HCl via Granulation with Its Paracellular Pathway Enhancer Using Factorial Experimental Design
title_short An Industrial Procedure for Pharmacodynamic Improvement of Metformin HCl via Granulation with Its Paracellular Pathway Enhancer Using Factorial Experimental Design
title_sort industrial procedure for pharmacodynamic improvement of metformin hcl via granulation with its paracellular pathway enhancer using factorial experimental design
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8576103/
https://www.ncbi.nlm.nih.gov/pubmed/34764634
http://dx.doi.org/10.2147/DDDT.S328262
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