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Gliclazide Microcrystals Prepared by Two Methods of In Situ Micronization: Pharmacokinetic Studies in Diabetic and Normal Rats

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Abstract

The low water-solubility of gliclazide (GL) leads to a low dissolution rate and variable bioavailability. The aim of this study was to investigate the effect of micronization on the absorption and pharmacokinetics of GL after oral administration in rats. GL microcrystals were prepared using solvent-change and pH-shift methods. Scanning electron microscopy showed considerable changes in the shape and size of crystals using both methods. In the optimized formulation of each method, the particle size of treated GL was reduced about 30 (from 290 to 9.9 μm) and 61 times (to 4.76 μm) by solvent-change and pH-shift methods, respectively. Recrystallized samples showed faster dissolution rate than untreated GL particles. Glucose-lowering effect, C max, and area under the drug concentration-time profile (area under the curve (AUC)) were compared in diabetic and normal rats. AUC and C max were increased by microcrystals in both groups of animals. Administration of 40 mg/kg of GL in the form of untreated drug and microcrystals obtained by solvent-change and pH-shift methods caused 12.49% and 21.04% enhancement in glucose-lowering effect of GL in diabetic rats, respectively.

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References

  1. Orienti I, Bigucci F, Luppi B, Cerchiara T, Zuccari G, Giunchedi P et al. Polyvinylalcohol substituted with triethyleneglycolmonoethylether as a new material for preparation of solid dispersion of hydrophobic drugs. Eur J Pharm Biopharm. 2002;54:229–33.

    Article  CAS  PubMed  Google Scholar 

  2. Lobenberg R, Amidon GL. Modern bioavailability, bioequivalence and biopharmaceutics classification system. New scientific approaches to international regulatory standards. Eur J Pharm Biopharm. 2000;50:3–12.

    Article  CAS  PubMed  Google Scholar 

  3. Sarkari M, Brown J, Chen X, Swinnea S, William RO, Johnston KP. Enhanced drug dissolution using evaporative precipitation into aqueous solution. Int J Pharm. 2002;243:17–31.

    Article  CAS  PubMed  Google Scholar 

  4. Gibson M. Pharmaceutical preformulation and formulation—a practical guide from candidate drug selection to commercial dosage form. Englewood: HIS Health Group; 2001.

    Google Scholar 

  5. Kim ST, Kwon JH, Lee JJ, Kim CW. Microcrystallization of indomethacin using a pH-shift method. Int J Pharm. 2003;263(1–2):141–50.

    Article  CAS  PubMed  Google Scholar 

  6. Chaumeil JC. Micronization: a method of improving the bioavailability of poorly soluble drugs. Meth Find Exp Clin Pharmacol. 1998;20:211–5.

    CAS  Google Scholar 

  7. Rasenack N, Muller BW. Dissolution rate enhancement by in situ micronization of poorly water-soluble drugs. Pharm Res. 2002;19(12):1894–900.

    Article  CAS  PubMed  Google Scholar 

  8. Steckel H, Rasenack N, Muller BW. In situ micronization of disodiumcromoglycate for pulmonary delivery. Eur J Pharm Biopharm. 2003;55:173–80.

    Article  CAS  PubMed  Google Scholar 

  9. Williams III RO, Brown J, Liu J. Influence of micronization method on the performance of a suspension triamcinolone acetonide pressurized metered-dose inhaler formulation. Pharm Dev Tech. 1999;4(2):167–79.

    Article  CAS  Google Scholar 

  10. Huang QP, Wang JX, Chen GZ, Shen ZG, Chen JF, Yun J. Micronization of gemfibrozil by reactive precipitation process. Int J Pharm. 2008;360:58–64.

    Article  CAS  PubMed  Google Scholar 

  11. Zhang HX, Wang JX, Zhang ZB, Le Y, Shen ZG, Chen JF. Micronization of atorvastatin calcium by antisolvent precipitation process. Int J Pharm. 2009;374(1–2):106–13.

    Article  CAS  PubMed  Google Scholar 

  12. Giry K, Pean JM, Giraud L, Marsas S, Rolland H, Wuthrich P. Drug/lactose co-micronization by jet milling to improve aerosolization properties of a powder for inhalation. Int J Pharm. 2006;321:162–6.

    Article  CAS  PubMed  Google Scholar 

  13. Moribe K, Tsutsumi S, Morishita S, Shinozaki H, Tozuka Y, Oguchi T et al. Micronization of phenylbutazone by rapid expansion of supercritical CO2 solution. Chem Pharm Bull. 2005;53(8):1025–8.

    Article  CAS  PubMed  Google Scholar 

  14. Betageri GV, Makarla KR. Enhancement of dissolution of glyburide by solid dispersion and lyophylization techniques. Int J Pharm. 1995;126:155–60.

    Article  CAS  Google Scholar 

  15. Palmer KJ, Brogden RN. Gliclazide. An update of its pharmacological properties and therapeutic efficacy in non-insulin-dependent diabetes mellitus. Drugs. 1993;46:93–125.

    Article  Google Scholar 

  16. Arias-Blanco MJ, Moyano JR, Perez-Martinez JI, Gines JM. Study of the inclusion of GL in α-cyclodextrin. J Pharm Biomed Anal. 1998;18:275–9.

    Article  CAS  PubMed  Google Scholar 

  17. Ozkan Y, Atay T, Dikmen N, Isimer A, Aboul-Enein HY. Improvement of water solubility and in vitro dissolution rate of GL by complexation with β-cyclodextrin. Pharm Act Helv. 2000;74:365–70.

    Article  CAS  Google Scholar 

  18. Aggarwal S, Singh PN, Mishra B. Studies on solubility and hypoglycemic activity of gliclazide beta-cyclodextrin-hydroxypropylmethylcellulose complexes. Pharmazie. 2002;57(3):191–3.

    CAS  PubMed  Google Scholar 

  19. Moyano JR, Arias-Blanco MJ, Gines JM, Rabasco AM, Perez-Martinez JI, Mor M et al. Nuclear magnetic resonance investigation of the inclusion complexation of GL with β-cyclodextrin. J Pharm Sci. 1997;86(1):72–5.

    Article  CAS  PubMed  Google Scholar 

  20. Varshosaz J, Talari R, Mostafavi A, Nokhodchi A. Dissolution enhancement of gliclazide using in situ micronization by solvent change method. Powder Tech. 2008;187:222–30.

    Article  CAS  Google Scholar 

  21. Talari R, Varshosaz J, Mostafavi A, Nokhodchi A. Dissolution enhancement of gliclazide using pH change approach in Presence of Twelve Stabilizers with Various Physico-Chemical Properties. J Pharm Pharmaceutic Sci. 2009;12(3):250–65.

    CAS  Google Scholar 

  22. Rouini MR, Mohajer A, Tahami MH. A simple and sensitive HPLC method for determination of gliclazide in human serum. J Chromatography B. 2003;785:383–6.

    Article  CAS  Google Scholar 

  23. Jaiswal D, Rai PK, Kumar A, Mehta S, Watal G. Effect of Moringa oleifera Lam. Leaves aqueous extract therapy on hyperglycemic rats. J Ethnopharmacol. 2009;123(3):392–6.

    Article  PubMed  Google Scholar 

  24. Weiss J, Taylor GR, Zimmermann F, Nebendahl K. Collection of body fluids. In: Krinke GJ, editor. The handbook of experimental animals, the laboratory rat. San Diego: Academic; 2000. p. 488–9.

    Google Scholar 

  25. Gibaldi M, Perrier D. Pharmacokinetics. 2nd ed. New York: Marcel Dekker; 1982. p. 149–51.

    Google Scholar 

  26. Pandikumar P, Prakash Babu N, Ignacimuthu S. Hypoglycemic and antihyperglycemic effect of Begonia malabarica Lam. in normal and streptozotocin induced diabetic rats. J Ethnopharmacol. 2009;124:111–5.

    Article  CAS  PubMed  Google Scholar 

  27. Kuo CY, Wu SM. High-performance liquid chromatography with electrochemical detection for analysis of gliclazide in plasma. J Chromatogr A. 2005;1088:131–5.

    Article  CAS  PubMed  Google Scholar 

  28. Poirier JM, Perez M, Cheymol G. High-performance liquid chromatographic determination of gliclazide in human plasma. J Chromatogr. 1987;421:223–6.

    Article  CAS  PubMed  Google Scholar 

  29. Charles BG, Ravenscroft PJ. Measurement of gliclazide in plasma by radial compression reversed-phase liquid chromatography. Clin Chem. 1984;30:1789–91.

    CAS  PubMed  Google Scholar 

  30. Yu NH, Ho ENM, Tang FPW, Wan TSM, Wong ASY. Comprehensive screening of acidic and neutral drugs in equine plasma by liquid chromatography–tandem mass spectrometry. J Chrom A. 2008;1189:426–34.

    Article  CAS  Google Scholar 

  31. Varshosaz J, Tavakoli N, Minayian M, Rahdari N. Applying the Taguchi design for optimized formulation of sustained-release gliclazide chitosan beads: an in vitro/in vivo study. AAPS Pharm Sci Tech. 2009;10(1):158–65.

    Article  CAS  Google Scholar 

  32. Tanira MOM, Furman BL. The in vivo interaction between gliclazide and glibenclamide and insulin on glucose disposal in the rat. Pharmacol Res. 1999;39:349–56.

    Article  CAS  PubMed  Google Scholar 

  33. Gholamhoseinian A, Fallah H, Sharififar F. Inhibitory effect of methanol extract of Rosa damascena Mill. Flowers on α-glucosidase activity and postprandial hyperglycemia in normal and diabetic rats. Phytomedicine. 2009;16(10):935–41.

    Article  CAS  PubMed  Google Scholar 

  34. Cunha WR, Arantes GM, Ferreira DS, Lucarini R, Silva MLA, Furtado NAJC et al. Hypoglycemic effect of Leandra lacunosa in normal and alloxan-induced diabetic rats. Fitoterapia. 2008;79:356–60.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgment

This work was supported by the Vice Chancellor of Research of Isfahan University of Medical Sciences for financial support of this project.

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Authors and Affiliations

  1. Department of Pharmaceutics, School of Pharmacy and Pharmaceutical Sciences, and Isfahan Pharmaceutical Sciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

    Roya Talari, Jaleh Varshosaz & Saied Abolfazl Mostafavi

  2. Medway School of Pharmacy, The Universities of Kent and Greenwich, Central Ave., Chathman Maritime, Kent, ME4 4TB, UK

    Ali Nokhodchi

  3. Food and Drug Laboratories Research Center, Tehran, Iran

    Roya Talari

  4. Drug Applied Research Center and Faculty of Pharmacy, Tabriz Medical Sciences University, Tabriz, Iran

    Ali Nokhodchi

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  1. Roya Talari
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  2. Jaleh Varshosaz
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  3. Saied Abolfazl Mostafavi
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  4. Ali Nokhodchi
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Correspondence to Jaleh Varshosaz.

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Talari, R., Varshosaz, J., Mostafavi, S.A. et al. Gliclazide Microcrystals Prepared by Two Methods of In Situ Micronization: Pharmacokinetic Studies in Diabetic and Normal Rats. AAPS PharmSciTech 11, 786–792 (2010). https://doi.org/10.1208/s12249-010-9441-9

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  • DOI: https://doi.org/10.1208/s12249-010-9441-9

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