Serum Concentrations and Hypoglycemic Effect of Gliclazide:Crosspovidone Solid Dispersion on Streptozotocin Induced Diabetic Rats

 

 Permissions and Reprints

Abstract

Gliclazide is practically insoluble in water and its GI absorption is limited by its dissolution rate. Our previously published works indicated that preparing gliclazide-crosspovidone solid dispersion in the drug/ carrier ratio of 1:1 using cogrinding technique is able to enhance drug dissolution rate. The coground of gliclazide-crosspovidone was administrated to the rats and the hypoglycemic effects of pure drug, a physical mixture and the coground were considered in 3 groups of rats weighing 200–250 g (n=6). The rats were made diabetic by single intravenous administration of streptozotocin (60 mg/kg). Each of the rats received a single dose of gliclazide (equivalent to 40 mg/kg) as pure drug, physical mixture and coground in an aqueous suspension. Glucose level was assessed via glucometer after collecting the blood samples from tail vein. Gliclazide concentration in plasma was assessed applying high pressure liquid chromatography. According to 1-way ANOVA, Student–Newman–Keuls test, the coground revealed enhanced hypoglycemic effects as well as higher serum gliclazide concentration relative to pure drug and its corresponding physical mixture in the all sampling times. The area under serum glucose concentration curve vs. time for the pure gliclazide, physical mixture and coground formulations were 3 090.5±79, 3 018.8±96 and 2 374.0±73 mg.h/dl, respectively. Correspondingly, their area under serum gliclazide concentration curve vs. time were 1 171.8±156.8, 1 379.5±96.2 and 4 827.7±637.5 μg.h/ml. It follows that; formulation of gliclazide-crosspovidone coground is able to improve oral absorption of the drug.

• References

• 1 Palmer KJ, Brogden RN. Gliclazide. An update of its pharmacological properties and therapeutic efficacy in non-insulin-dependent diabetes mellitus. Drugs 1993; 46: 92-125
  CrossrefPubMedGoogle Scholar
• 2 Harrower AD. Comparison of efficacy, secondary failure rate, and complications of sulfonylureas. J Diabetes Complications 1994; 8: 201-203
  CrossrefPubMedGoogle Scholar
• 3 Campbell DB, Lavielle R, Nathan C. The mode of action and clinical pharmacology of gliclazide: a review. Diabetes Res Clin Pract 1991; 14 (Suppl. 02) S21-S36
  CrossrefPubMedGoogle Scholar
• 4 Delrat P, Paraire M, Jochemsen R. Complete bioavailability and lack of food-effect on pharmacokinetics of gliclazide 30 mg modified release in healthy volunteers. Biopharm Drug Dispos 2002; 23: 151-157
  CrossrefPubMedGoogle Scholar
• 5 Asyarie S, Rachmawati H. In vivo and in vitro evaluation of a solid dispersion system of gliclazide:PEG 6000. PDA J Pharm Sci Technol 2007; 61: 400-410
  PubMedGoogle Scholar
• 6 Kubo H, Osawa T, Takashima K et al. Enhancement of oral bioavailability and pharmacological effect of 1-(3,4-dimethoxyphenyl)-2,3-bis(methoxycarbonyl)-4-hydroxy-6,7,8-trimethoxynaphthalene (TA-7552), a new hypocholesterolemic agent, by micronization in co-ground mixture with D-mannitol. Biol Pharm Bull 1996; 19: 741-747
  CrossrefPubMedGoogle Scholar
• 7 Martis L, Hall NA, Thakkar AL. Micelle formation and testosterone solubilization by sodium glycocholate. J Pharm Sci 1972; 61: 1757-1761
  CrossrefPubMedGoogle Scholar
• 8 Rees JA, Collett JH. The dissolution of salicylic acid in micellar solutions of polysorbate 20. J Pharm Pharmacol 1974; 26: 956-960
  CrossrefPubMedGoogle Scholar
• 9 Barzegar-Jalali M, Valizadeh H, Siahi Shadbad MR et al. Cogrinding as an approach to enhance dissolution rate of a poorly water-soluble drug (gliclazide). Powder Technology 2010; 197: 150-158
  CrossrefPubMedGoogle Scholar
• 10 Javadzadeh Y, Siahi MR, Asnaashari S et al. An investigation of physicochemical properties of piroxicam liquisolid compacts. Pharm Dev Technol 2007; 12: 337-343
  CrossrefPubMedGoogle Scholar
• 11 Javadzadeh Y, Siahi MR, Asnaashari S et al. Liquisolid technique as a tool for enhancement of poorly water-soluble drugs and evaluation of their physicochemical properties. Acta Pharm 2007; 57: 99-109
  PubMedGoogle Scholar
• 12 Spireas S, Wang T, Grover R. Effect of powder substrate on the dissolution properties of methyclothiazide liquisolid compacts. Drug Dev Ind Pharm 1999; 25: 163-168
  CrossrefPubMedGoogle Scholar
• 13 Kapsi SG, Ayres JW. Processing factors in development of solid solution formulation of itraconazole for enhancement of drug dissolution and bioavailability. Int J Pharm 2001; 229: 193-203
  CrossrefPubMedGoogle Scholar
• 14 Barzegar-Jalali M, Nayebi AM, Valizadeh H et al. Evaluation of in vitro-in vivo correlation and anticonvulsive effect of carbamazepine after cogrinding with microcrystalline cellulose. J Pharm Pharm Sci 2006; 9: 307-316
  PubMedGoogle Scholar
• 15 Mohammadi G, Barzegar-Jalali M, Valizadeh H et al. Reciprocal powered time model for release kinetic analysis of ibuprofen solid dispersions in oleaster powder, microcrystalline cellulose and crospovidone. J Pharm Pharm Sci 2010; 13: 152-161
  PubMedGoogle Scholar
• 16 Valizadeh H, Zakeri-Milani P, Barzegar-Jalali M et al. Preparation and characterization of solid dispersions of piroxicam with hydrophilic carriers. Drug Dev Ind Pharm 2007; 33: 45-56
  CrossrefPubMedGoogle Scholar
• 17 Kapsi SG, Ayres JW. Processing factors in development of solid solution formulation of itraconazole for enhancement of drug dissolution and bioavailability. Int J Pharm 2001; 229: 193-203
  CrossrefPubMedGoogle Scholar
• 18 Craig DQ.. The mechanisms of drug release from solid dispersions in water-soluble polymers. Int J Pharm 2002; 231: 131-144
  CrossrefPubMedGoogle Scholar
• 19 Biswal S, Sahoo J, Murthy PN et al. Enhancement of dissolution rate of gliclazide using solid dispersions with polyethylene glycol 6000. AAPS PharmSciTech 2008; 9: 563-570
  CrossrefPubMedGoogle Scholar
• 20 Craig DQ. The mechanisms of drug release from solid dispersions in water-soluble polymers. Int J Pharm 2002; 231: 131-144
  CrossrefPubMedGoogle Scholar
• 21 Ohara T, Kitamura S, Kitagawa T et al. Dissolution mechanism of poorly water-soluble drug from extended release solid dispersion system with ethylcellulose and hydroxypropylmethylcellulose. Int J Pharm 2005; 302: 95-102
  CrossrefPubMedGoogle Scholar
• 22 Ruan LP, Yu BY, Fu GM et al. Improving the solubility of ampelopsin by solid dispersions and inclusion complexes. J Pharm Biomed Anal 2005; 38: 457-464
  CrossrefPubMedGoogle Scholar
• 23 Verheyen S, Blaton N, Kinget R et al. Mechanism of increased dissolution of diazepam and temazepam from polyethylene glycol 6 000 solid dispersions. Int J Pharm 2002; 249: 45-58
  CrossrefPubMedGoogle Scholar
• 24 Barzegar-Jalali M, Nayebi AM, Valizadeh H et al. Evaluation of in vitro-in vivo correlation and anticonvulsive effect of carbamazepine after cogrinding with microcrystalline cellulose. J Pharm Pharm Sci 2006; 9: 307-316
  PubMedGoogle Scholar
• 25 Vogt M, Vertzoni M, Kunath K et al. Cogrinding enhances the oral bioavailability of EMD 57033, a poorly water soluble drug, in dogs. Eur J Pharm Biopharm 2008; 68: 338-345
  CrossrefPubMedGoogle Scholar
• 26 Vogt M, Kunath K, Dressman JB. Dissolution enhancement of fenofibrate by micronization, cogrinding and spray-drying: comparison with commercial preparations. Eur J Pharm Biopharm 2008; 68: 283-288
  CrossrefPubMedGoogle Scholar
• 27 Vogt M, Kunath K, Dressman JB. Dissolution improvement of four poorly water soluble drugs by cogrinding with commonly used excipients. Eur J Pharm Biopharm 2008; 68: 330-337
  CrossrefPubMedGoogle Scholar
• 28 Wongmekiat A, Tozuka Y, Oguchi T et al. Formation of fine drug particles by cogrinding with cyclodextrins. I. The use of beta-cyclodextrin anhydrate and hydrate. Pharm Res 2002; 19: 1867-1872
  CrossrefPubMedGoogle Scholar
• 29 Asyarie S, Rachmawati H. In vivo and in vitro evaluation of a solid dispersion system of gliclazide:PEG 6000. PDA J Pharm Sci Technol 2007; 61: 400-410
  PubMedGoogle Scholar
• 30 Park JY, Kim KA, Kim SL et al. Quantification of gliclazide by semi-micro high-performance liquid chromatography: application to a bioequivalence study of two formulations in healthy subjects. J Pharm Biomed Anal 2004; 35: 943-949
  CrossrefPubMedGoogle Scholar
• 31 Armitage P. Statistical methods in medical research. London: Blackwell Scientific Publications; 1997
  Google Scholar
• 32 Asyarie S, Rachmawati H. In vivo and in vitro evaluation of a solid dispersion system of gliclazide:PEG 6000. PDA J Pharm Sci Technol 2007; 61: 400-410
  PubMedGoogle Scholar
• 33 Park JY, Kim KA, Kim SL et al. Quantification of gliclazide by semi-micro high-performance liquid chromatography: application to a bioequivalence study of two formulations in healthy subjects. J Pharm Biomed Anal 2004; 35: 943-949
  CrossrefPubMedGoogle Scholar
• 34 Asyarie S, Rachmawati H. In vivo and in vitro evaluation of a solid dispersion system of gliclazide:PEG 6000. PDA J Pharm Sci Technol 2007; 61: 400-410
  PubMedGoogle Scholar