Glibenclamide Mini-tablets with an Enhanced Pharmacokinetic and Pharmacodynamic Performance
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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.
KEY WORDSglibenclamide 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
absorption rate constant
elimination rate constant
limit of detection
limit of quantitation
mean residence time
relative standard deviation
- t½ (abs)
- t½ (el.)
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.
- 1.Glyburide dosage guide with precautions. http://www.drugs.com. Accessed 1 Dec 2017.
- 3.Obaidat AA, Ababneh NM. Improvement of glibenclamide bioavailability using cyclodextrin inclusion complex dispersed in polyethylene glycol. Jordan J Pharm Sci. 2009;2:119–30.Google Scholar
- 5.Aleksovski A, Dreu R, Gasperlin M, Planinsek O. Mini-tablets: a contemporary system for oral drug delivery in targeted patient groups. Expert Opin Drug Deliv. 2014;12:1–20.Google Scholar
- 13.Aboutaleb AE, Abdel-Rahman SI, Ahmed MO, Younis MA. Enhancement of domperidone dissolution rate via formulation of adsorbates and co-adsorbates. Int J Pharm Sci Res. 2016;7:951–60.Google Scholar
- 14.Abou-Taleb AE, Abdel-Rhman AA, Samy EM, Tawfeek HM. Formulation and evaluation of rofecoxib tablets in comparison with marketed product. Saudi Pharm J. 2006;14:187–95.Google Scholar
- 15.Abou-Taleb AE, Abdel-Rhman AA, Samy EM, Tawfeek HM. Formulation and evaluation of rofecoxib capsules. Saudi Pharm J. 2009;17:40–50.Google Scholar
- 23.Moore JW, Flanner HH. Mathematical comparison of curves with an emphasis on dissolution profiles. Pharm Technol. 1996;20:64–74.Google Scholar
- 27.The USP Pharmacopeia 35 and the National Formularity 30. Rockville, MD 20852-1790 USA. 2012, P 420.Google Scholar
- 28.Abdel Rahman AA, Khidr SH, Samy EM, Sayed MA. Enhancement of the dissolution rate of glipizide capsules using fenugreek as natural additive. Unique J Pharm Biol Sci. 2014;2:1–8.Google Scholar
- 29.Alam SA, Khan AH, Sirhindi GA, Khan S. Alloxan induced diabetes in rabbits. Pak J Pharmacol. 2005;22:41–5.Google Scholar
- 30.Rajasekaran UB, Nayak US. How to choose drug dosage for human experiments based on drug dose used on animal experiments: a review. IJSS Case Rep Rev. 2014;1:31–2.Google Scholar
- 31.Food and Drug Administration (FDA). Guidance for industry: bioanalytical method validation. USA: US Department of health and human services; 2013.Google Scholar
- 32.Daksh S, Goyal A, Pandiya CK. Validation of analytical methods—strategies & significance. Int J Res Dev Pharm Life Sci. 2015;4:1489–97.Google Scholar
- 34.Aboutaleb AE, Abdel-Rahman SI, Ahmed MO, Younis MA. Formulation of domperidone in gastro-retentive floating tablets. J Innovations Pharm Biol Sci. 2016;3:81–93.Google Scholar
- 35.Rockwood Ltd. Laponite: the performance enhancer. http://www.prochem.ch/html/forum/forumbeilagen0107/Laponite_RW_broch_e.pdf. Accessed 31 Mar 2016.
- 38.Evonik Resource Efficiency GmbH. Product information AEROSIL® 200. https://www.aerosil.com/www2/uploads/productfinder/AEROSIL-200-EN.pdf. Accessed 22 Feb 2016.
- 40.Makhlof A. Formulation and evaluation of solid pharmaceutical dosage forms containing glipizide. M.Sc. thesis, Faculty of Pharmacy, Assiut University, Assiut, Egypt; 2004.Google Scholar
- 43.Mahato RI, Narang AS. Interfacial phenomena. In: Pharmaceutical dosage forms and drug delivery. 2nd ed. New York: CRC Press; 2012. p. 160.Google Scholar
- 45.Ismail A, Saleh KI, Ibrahim MA, Khalaf S. Effect of porous silica as a drug carrier on the release rate of naproxen from emulgel. Bull Pharm Sci Assiut Univ. 2006;29:224–35.Google Scholar
- 46.Samy AM, Kassem AA, Samy EM, Abu-elyazid SK, Hassan YA. Development and characterization of celecoxib floating capsules. J Life Med. 2014;2:95–110.Google Scholar
- 50.Girolamo GD, Opezzo JAW, Lopez MI, Schere D, Keller G, Gonzalez CD, et al. Relative bioavailability of new formulation of paracetamol effervescent powder containing sodium bicarbonate versus paracetamol tablets: a comparative pharmacokinetic study in fed subjects. Expert Opin Pharmacother. 2007;8:2449–57.CrossRefGoogle Scholar