Advertisement

AAPS PharmSciTech

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

Glibenclamide Mini-tablets with an Enhanced Pharmacokinetic and Pharmacodynamic Performance

  • Hesham M. Tawfeek
  • Matthew Roberts
  • Mohamed A. El Hamd
  • Ahmed A. H. Abdellatif
  • Mahmoud A. Younis
Research Article
  • 491 Downloads

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.

KEY WORDS

glibenclamide co-adsorbates mini-tablets pharmacodynamics oral bioavailability 

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

Cmax

maximum (peak) drug concentration in plasma

ClT

total drug clearance

DSC

differential scanning calorimetry

FR

relative bioavailability

GLC

glibenclamide

IS

internal standard

Kabs

absorption rate constant

Kel

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

t½ (abs)

absorption half-life

t½ (el.)

elimination half-life

Tmax

time to achieve peak drug concentration in plasma

Notes

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.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Glyburide dosage guide with precautions. http://www.drugs.com. Accessed 1 Dec 2017.
  2. 2.
    Shazly GA, Mahrous GM. Assessment of the physicochemical properties and in vitro dissolution of glibenclamide tablets marketed in Saudi Arabia. Dissolut Technol. 2014;21:61–6.CrossRefGoogle Scholar
  3. 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
  4. 4.
    Roden DF, Altman KW. Causes of dysphagia among different age groups: a systematic review of the literature. Otolaryngol Clin North Am. 2013;46:965–87.CrossRefGoogle Scholar
  5. 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
  6. 6.
    Kawakami K, Oda N, Miyoshi K, Funaki T, Ida Y. Solubilization behavior of a poorly soluble drug under combined use of surfactants and cosolvents. Eur J Pharm Sci. 2006;28:7–14.CrossRefGoogle Scholar
  7. 7.
    Ruan LP, Yu BY, Fu GM, Zhu DN. Improving the solubility of ampelopsin by solid dispersions and inclusion complexes. J Pharm Biomed Anal. 2005;38:457–64.CrossRefGoogle Scholar
  8. 8.
    Aboutaleb AE, Abdel-Rahman SI, Ahmed MO, Younis MA. Improvement of domperidone solubility and dissolution rate by dispersion in various hydrophilic carriers. J App Pharm Sci. 2016;6:133–9.CrossRefGoogle Scholar
  9. 9.
    Balata GF, Essa EA, Shamardl HA, Zaidan SH, Abourehab MAS. Self-emulsifying drug delivery systems as a tool to improve solubility and bioavailability of resveratrol. Drug Design Dev Ther. 2016;10:117–28.CrossRefGoogle Scholar
  10. 10.
    Hu L. Prodrugs: effective solutions for solubility, permeability and targeting challenges. IDrugs. 2004;7:736–42.PubMedGoogle Scholar
  11. 11.
    Shazly GA, Alshehri S, Ibrahim MA, Tawfeek HM, Razik JA, Hassan YA, et al. Development of domepridone solid lipid nanoparticles: in vitro and in vivo characterization. AAPS PharmSciTec. 2018;19:1712–9.  https://doi.org/10.1208/s12249-018-0987-2.CrossRefGoogle Scholar
  12. 12.
    Tatavarti AS, Hoag SW. Microenvironmental pH modulation based release enhancement of a weakly basic drug from hydrophilic matrices. J Pharm Sci. 2006;95:1459–68.CrossRefGoogle Scholar
  13. 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. 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. 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
  16. 16.
    Caputo G. Supercritical fluid adsorption of domperidone on silica aerogel. Adv Chem Eng Sci. 2013;3:189–94.CrossRefGoogle Scholar
  17. 17.
    Hadi MA, Rao NGR, Rao AS. Formulation and evaluation of pH-responsive mini-tablets for ileo-colonic targeted drug delivery. Trop J Pharm Res. 2014;13:1021–9.CrossRefGoogle Scholar
  18. 18.
    Mohamed FAA, Roberts M, Seton L, Ford JL, Levina M, Rajabi Siahboomi AR. The influence of HPMC concentration on release of theophylline or hydrocortisone from extended release minitablets. Drug Dev Ind Pharm. 2013;39:1167–74.CrossRefGoogle Scholar
  19. 19.
    Tawfeek HM, Saleem IY, Roberts M. Dissolution enhancement and formulation of rapid-release lornoxicam mini-tablets. J Pharm Sci. 2014;103:2470–83.CrossRefGoogle Scholar
  20. 20.
    Sasaki H, Sunagawa Y, Takahashi K, Imaizumi A, Fukuda H, Hashimoto T, et al. Innovative preparation of curcumin for improved oral bioaviability. Biol Pharm Bull. 2011;34:660–5.CrossRefGoogle Scholar
  21. 21.
    Seedher N, Kanojia M. Micellar solubilization of some poorly soluble antidiabetic drugs: a technical note. AAPS PharmSciTech. 2008;9:431–6.CrossRefGoogle Scholar
  22. 22.
    Qian F, Tao J, Desikan S, Hussain M, Smith RL. Mechanistic investigation of Pluronic R based nanocrystalline drug–polymer solid dispersions. Pharm Res. 2007;24:1551–60.CrossRefGoogle Scholar
  23. 23.
    Moore JW, Flanner HH. Mathematical comparison of curves with an emphasis on dissolution profiles. Pharm Technol. 1996;20:64–74.Google Scholar
  24. 24.
    Mendyk A, Pacławski A, Szlęk J, Jachowicz R. PhEq_bootstrap: an open source software for simulation of f2 distribution in cases of a large variability in the dissolution profiles. Dissolut Technol. 2013;20:13–7.CrossRefGoogle Scholar
  25. 25.
    Mohamed FAA, Roberts M, Seton L, Ford JL, Levina M, Rajabi-Siahboomi AR. Production of extended release mini-tablets using directly compressible grades of HPMC. Drug Dev Ind Pharm. 2013;39:1690–7.CrossRefGoogle Scholar
  26. 26.
    Fell J, Newton JM. The tensile strength of lactose tablets. J Pharm Pharmacol. 1968;20:657–9.CrossRefGoogle Scholar
  27. 27.
    The USP Pharmacopeia 35 and the National Formularity 30. Rockville, MD 20852-1790 USA. 2012, P 420.Google Scholar
  28. 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. 29.
    Alam SA, Khan AH, Sirhindi GA, Khan S. Alloxan induced diabetes in rabbits. Pak J Pharmacol. 2005;22:41–5.Google Scholar
  30. 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. 31.
    Food and Drug Administration (FDA). Guidance for industry: bioanalytical method validation. USA: US Department of health and human services; 2013.Google Scholar
  32. 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
  33. 33.
    Aboutaleb AE, Abdel-Rahman SI, Ahmed MO, Younis MA. Design and evaluation of domperidone sublingual tablets. Int J Pharm Pharm Sci. 2016;8:195–201.CrossRefGoogle Scholar
  34. 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. 35.
    Rockwood Ltd. Laponite: the performance enhancer. http://www.prochem.ch/html/forum/forumbeilagen0107/Laponite_RW_broch_e.pdf. Accessed 31 Mar 2016.
  36. 36.
    Chen X. Modeling of experimental adsorption isotherm data. Information. 2015;6:14–22.CrossRefGoogle Scholar
  37. 37.
    Lou H, Liu M, Wang L, Mishra SR, Qu W, Johnson J, et al. Development of a mini-tablet of co-grinded prednisone–Neusilin complex for pediatric use. AAPS PharmSciTech. 2013;14:950–8.CrossRefGoogle Scholar
  38. 38.
    Evonik Resource Efficiency GmbH. Product information AEROSIL® 200. https://www.aerosil.com/www2/uploads/productfinder/AEROSIL-200-EN.pdf. Accessed 22 Feb 2016.
  39. 39.
    Sharma S, Sher P, Badve S, Pawar AP. Adsorption of meloxicam on porous calcium silicate: characterization and tablet formulation. AAPS PharmSciTech. 2005;6:E618–25.CrossRefGoogle Scholar
  40. 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
  41. 41.
    McCarthy CA, Ahren RJ, Dontireddy R, Ryan KB, Crean AM. Mesoporous silica formulation strategies for drug dissolution enhancement: a review. Expert Opin Drug Deliv. 2016;13:93–108.CrossRefGoogle Scholar
  42. 42.
    Ahuja G, Pathak K. Porous carriers for controlled/modulated drug delivery. Indian J Pharm Sci. 2009;71:599–607.CrossRefGoogle Scholar
  43. 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
  44. 44.
    Vadher AH, Parikh JR, Parikh RH, Solanki AB. Preparation and characterization of co-grinded mixture of aceclofenac and NEU US2 for dissolution enhancement of aceclofenac. AAPS PharmSciTech. 2009;10:606–14.CrossRefGoogle Scholar
  45. 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. 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
  47. 47.
    Saha S, Shahiwala AF. Multifunctional coprocessed excipients for improved tabletting performance. Expert Opin Drug Deliv. 2009;6:197–208.CrossRefGoogle Scholar
  48. 48.
    Hauschild K, Picker KM. Evaluation of a new co-processed compound based on lactose and maize starch for tablet formulation. AAPS Pharm Sci. 2004;6:27–38.CrossRefGoogle Scholar
  49. 49.
    Cherkaoui I, Monticone V, Vaution C, Treiner C. Coadsorption of the sodium salts of two steroid molecules at a silica/interface as induced by the adsorption of a cationic surfactant. Int J Pharm. 2000;201:71–7.CrossRefGoogle Scholar
  50. 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

Copyright information

© American Association of Pharmaceutical Scientists 2018

Authors and Affiliations

  • Hesham M. Tawfeek
    • 1
    • 2
  • 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

Personalised recommendations