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Glibenclamide Mini-tablets with an Enhanced Pharmacokinetic and Pharmacodynamic Performance

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Abstract

In an attempt to decrease the dose, anticipated side effects, and the cost of production of glibenclamide, GLC, a potent oral hypoglycemic drug, the enhancement of the dissolution and hence the oral bioavailability were investigated. Adsorption and co-adsorption techniques using carriers having a very large surface area and surface active agents were utilized to enhance the drug dissolution. Moreover, the Langmuir adsorption isotherms were constructed to identify the type and mechanism of adsorption. The optimized formulation showing the highest in vitro release was compressed into mini-tablet to facilitate drug administration to elderly patients and those having swallowing difficulties. The produced mini-tablets were tested for their mechanical strength and in vitro release pattern. In addition, the pharmacodynamic and pharmacokinetic studies in New Zealand rabbits were performed using the optimized mini-tablet formulation. Mini-tablets containing GLC co-adsorbate with Pluronic F-68 and Laponite RD showed 100 ± 1.88% of GLC released after 20 min. Pharmacodynamic studies in rabbits revealed significantly higher (p ≤ 0.05) hypoglycemic effect with the optimized mini-tablets at a lower GLC dose compared to mini-tablets containing the commercial GLC dose. Moreover, pharmacokinetic analysis showed significantly higher (p ≤ 0.05) AUC, Cmax, and shorter Tmax. The optimized mini-tablet formulation showed 1.5-fold enhancement of the oral bioavailability compared to mini-tablets containing untreated GLC. It could be concluded that the co-adsorption technique successfully enhanced the oral bioavailability of GLC. Furthermore, the produced mini-tablets have a higher oral bioavailability with a lower GLC dose, which could offer economic benefit for industry as well as acceptability for patients.

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Abbreviations

AUC(0–24 h) :

area under drug plasma concentration versus time curve from zero time to the end of the experiment

AUC(0–∞) :

area under drug plasma concentration versus time curve from zero time to infinity

AUMC(0–24 h) :

area under first moment curve from zero time to the end of the experiment

AUMC(0–∞) :

area under first moment curve from zero time to infinity

BCS:

biopharmaceutical classification system

C max :

maximum (peak) drug concentration in plasma

ClT :

total drug clearance

DSC:

differential scanning calorimetry

F R :

relative bioavailability

GLC:

glibenclamide

IS:

internal standard

K abs :

absorption rate constant

K el :

elimination rate constant

LOD:

limit of detection

LOQ:

limit of quantitation

MRT:

mean residence time

NUS:

Neusilin

PEG:

polyethylene glycol

RSD:

relative standard deviation

STZ:

streptozotocin

t ½ (abs) :

absorption half-life

t ½ (el.) :

elimination half-life

T max :

time to achieve peak drug concentration in plasma

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Acknowledgments

The authors are grateful to Faculty of Pharmacy, Assiut University, Egypt, for supporting and facilitating the research. The authors are also grateful to T3A Company for Pharmaceutical Industries, Assiut, Egypt, for gifting GLC and glipizide. The authors are grateful thankful to Dr. Hamzah Maswedeh, Department of Pharmaceutics, Faculty of Pharmacy, Qassim University, KSA.

Author information

Authors and Affiliations

  1. Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Mutah University, Mutah, Karak, 61710, Jordan

    Hesham M. Tawfeek

  2. Department of Industrial Pharmacy, Faculty of Pharmacy, Assiut University, Assiut, 71526, Egypt

    Hesham M. Tawfeek & Mahmoud A. Younis

  3. School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK

    Matthew Roberts

  4. Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Al-Azhar University, Assiut, 71524, Egypt

    Mohamed A. El Hamd

  5. Department of Pharmacy Practice, Faculty of Pharmacy, Shaqra University, Shaqraa, 11911, Kingdom of Saudi Arabia

    Mohamed A. El Hamd

  6. Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Al-Azhar University, Assiut, 71524, Egypt

    Ahmed A. H. Abdellatif

  7. Department of Pharmaceutics, Faculty of Pharmacy, Qassim University, Buraydah, Kingdom of Saudi Arabia

    Ahmed A. H. Abdellatif

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  1. Hesham M. Tawfeek
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Correspondence to Hesham M. Tawfeek.

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Tawfeek, H.M., Roberts, M., El Hamd, M.A. et al. Glibenclamide Mini-tablets with an Enhanced Pharmacokinetic and Pharmacodynamic Performance. AAPS PharmSciTech 19, 2948–2960 (2018). https://doi.org/10.1208/s12249-018-1108-y

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