AAPS PharmSciTech

, Volume 19, Issue 7, pp 2948–2960 | Cite as

Glibenclamide Mini-tablets with an Enhanced Pharmacokinetic and Pharmacodynamic Performance

  • Hesham M. TawfeekEmail author
  • Matthew Roberts
  • Mohamed A. El Hamd
  • Ahmed A. H. Abdellatif
  • Mahmoud A. Younis
Research Article


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.


glibenclamide co-adsorbates mini-tablets pharmacodynamics oral bioavailability 


AUC(0–24 h)

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


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


area under first moment curve from zero time to infinity


biopharmaceutical classification system


maximum (peak) drug concentration in plasma


total drug clearance


differential scanning calorimetry


relative bioavailability




internal standard


absorption rate constant


elimination rate constant


limit of detection


limit of quantitation


mean residence time




polyethylene glycol


relative standard deviation



t½ (abs)

absorption half-life

t½ (el.)

elimination half-life


time to achieve peak drug concentration in plasma



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.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.


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Copyright information

© American Association of Pharmaceutical Scientists 2018

Authors and Affiliations

  • Hesham M. Tawfeek
    • 1
    • 2
    Email author
  • Matthew Roberts
    • 3
  • Mohamed A. El Hamd
    • 4
    • 5
  • Ahmed A. H. Abdellatif
    • 6
    • 7
  • Mahmoud A. Younis
    • 2
  1. 1.Department of Pharmaceutics and Pharmaceutical Technology, Faculty of PharmacyMutah UniversityMutahJordan
  2. 2.Department of Industrial Pharmacy, Faculty of PharmacyAssiut UniversityAssiutEgypt
  3. 3.School of Pharmacy and Biomolecular SciencesLiverpool John Moores UniversityLiverpoolUK
  4. 4.Department of Pharmaceutical Analytical Chemistry, Faculty of PharmacyAl-Azhar UniversityAssiutEgypt
  5. 5.Department of Pharmacy Practice, Faculty of PharmacyShaqra UniversityShaqraaKingdom of Saudi Arabia
  6. 6.Department of Pharmaceutics and Industrial Pharmacy, Faculty of PharmacyAl-Azhar UniversityAssiutEgypt
  7. 7.Department of Pharmaceutics, Faculty of PharmacyQassim UniversityBuraydahKingdom of Saudi Arabia

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