ENHANCEMENT OF BIOAVAILABILITY OF GLIPIZIDE USING SOLID DISPERSIONS WITH GUM AEGLE MARMELOS
Keywords:Glipizide; Solid dispersion; Aegle marmelos; Solubility; Dissolution
Objective: The aim of the proposed study was formulation and in vitro/ vivo evolution of solid dispersions of glipizide with gum Aegle marmelos.
Methods: The phase solubility of glipizide in 0.1N HCl was investigated in the presence of different concentrations of gum Aegle marmelos. The solid dispersions (SDs) of glipizide with gum Aegle marmelos were formulated using solvent evaporation method at ratios of 1:1, 1:2, and 1:5 (glipizide: gum Aegle marmelos). Dissolution studies were conducted. The physicochemical characterization of the formulations was performed by using Fourier-transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC) and X-ray diffraction (XRD). Subsequently, bioavailability of pure glipizide, solid dispersion and marketed product was performed in rat.
Results: Glipizide solubility increased as the concentration of gum Aegle marmelos in 0.1N HCl was raised. The solubility study indicates spontaneous drug solubilization, which is supported by negative values of Gibb's free energy (ΔGotr). Glipizide rate of dissolution was increased in SDs containing gum, and the rate increased as the concentration of gum in the SDs increases. After preparing SDs and physical mixtures with gum, the mean dissolution time (MDT) of glipizide decreases considerably. FTIR spectroscopy study revealed that stability and the absence of a well-defined glipizide-gum interaction. The amorphous condition of glipizide in SDs of glipizide with gum was revealed by DSC and XRD studies.
Conclusion: The DSC and XRD studies indicate conversion of drug from crystalline to microcrystalline or amorphous form after formulation of solid dispersion with Aegle gum. The solid dispersion of glipizide with Aegle gum (893.04±25.5) showed better therapeutic activity compared to pure glipizide (535.65±11.5) and marketed formulation (767.5±13.6).
Chanda R, Ghosh A, Mitra T, Mohanty J, Pawankar G. Phytochemical and pharmacological activity of Aegle marmelos as a potential medicinal plant: An overview. The Internet Journal of Pharmacology 2007; Vol 6, No.1.
Jagetia GC and Baliga MS. The evaluation of nitric oxide scavenging activity of certain Indian medicinal plants in vitro: a preliminary study. Journal of Medicinal Food 2004; 7:343–348.
Kintzios SE. Terrestrial plant-derived anticancer agents and plant species used in anticancer research. Critical Reviews in Plant Sciences 2006; 25:79–113.
Baliga MS, Bhat HP, Joseph N and Fazal F. Phytochemistry and medicinal uses of the bael fruit (Aegle marmelos Correa): a concise review. Food Research International 2011; 44:1768–1775.
Anandharajan R, Jaiganesh S, Shankernarayanan NP, Viswakarma RA and Balakrishnan A. In vitro glucose uptake activity of Aeglesmarmelos and Syzygiumcumini by activation of Glut-4, P13 kinase and PPARy in L6 myotubes. Phytomedicine 2006; 13:434–441.
Kamalakkannan N and Prince PSM. Antihyperlipidaemic effect of Aegle marmelos fruit extract in streptozotocin-induced diabetes in rats. Journal of the Science of Food and Agriculture 2005; 85:569–573.
Choudhary Y, Saxena A, Kumar Y, Kumar S and Pratap V. Phytochemistry, pharmacological and traditional uses of Aegle marmelos. UHJPB 2017; 5:27–33.
Kamalakkannan N, Stanely P, Prince M. Hypoglycaemic effect of water extracts of Aegle marmelos fruits in streptozotocin diabetic rats. Journal of Ethnopharmacology 2003; 87: 207–210.
Prabir KM and Amal KM. The structure of bael (Aegle marmelos) gum. Carbohydrate Research 1980; 84(1):147-159.
Shirsand SB, Jonathan V, Potdar PS, Shirsand SS. Aegle marmelos as a disintegrant in design of fast dissolving tablets. Adv Nov Drug Deliv 2016; 1(1):7-11.
Joshi Y, Chaudhary RK, Teotia UVS. Formulation and Evaluation of Diclofenac Sodium Sustained Release Matrix Tablets Using Aegle Marmelos Gum. IJCTPR 2013;1(3):174-180.
Alam MT, Parvez N and Sharma PK. FDA-Approved Natural Polymers for Fast Dissolving Tablets. Journal of Pharmaceutics 2014; 1:1-6.
Ratnaparkhi MP, Chaudhari PD. Solubility enhancement of poorly water soluble drug using natural carrier. Int. Journal of Life Sciences and Pharma Research 2017; 7(3).
Murali Mohan GV, Prasad CDS, Ramana Murthy KV. Evaluation of modified gum karaya as carrier for the dissolution enhancement of poorly water-soluble drug nimodipine. Int J Pharm 2002; 234:1-7.
Varshini SS, Rajesh V. Fundamental aspects of a third component used in ternary solid dispersion: A review. Int J App Pharm 2021; 13(3):11-17.
Alkufi HK, Rashid AM. Enhancement of the solubility of Famotidine solid dispersion using natural polymer by solvent evaporation. Int J App Pharm 2021; 13(3):193-198.
Mallick S, Patra RK, Murthy PN. Current trends for preparation of solid dispersion. Research Journal of Pharmacy and Life Sciences 2020; 1(3):15-25.
Kim EJ, Chun MK, Jang JS and Choi HK. Preparation of a solid dispersion of felodipine using a solvent wetting method. Eur J Pharm and Biopharm 2006; 64(2):200-205.
Trapani G, Franco M, Latrofa A, Pantaleo MR, Provenzano MR, Sanna E, Maciocco E, Liso G. Physicochemical characterization and in vivo properties of Zolpidem in solid dispersions with polyethylene glycol 4000 and 6000. Int J Pharm 1999; 184:121–130.
Higuchi T, Connors K. Phase solubility techniques. Adv in Ana Chem. and Instrument 1965; 4:17–123.
Arias MJ, Gines JM, Moyano JR, Rabasco AM. Dissolution properties and in vivo behavior of Triamterene in solid dispersions with polyethylene glycols. Pharm Acta Helv 1996; 71:229–235.
Damian F, Blaton N, Naesens L, Balzarini J, Kinget R, Augustinjns P, Mooter GV. Physicochemical characterization of solid dispersions of the antiviral agent UC-781 with polyethylene glycol 6000 and Gelucire 44/14. Eur J of Pharm Sc 2000; 10:311–322.
Okonogi S, Oguchi T, Yonemochi E, Puttipipatkhachorn S, Yamamoto K. Improved dissolution of ofloxacin via solid dispersion. Int J of Pharm 1997a; 156:175–180.
Stepensky D, Friedman M, Srour W, Raz I, Hoffmana A. Preclinical evaluation of pharmacokinetic–pharmacodynamic rationale for oral CR metformin formulation. J Cont Rel 2001; 71:107–115.
Pepato MT, Keller EH, Baviera AM, Kettelhut IC, Vendarmini RC. Anti-diabetic activity of Bauhinia forficata decoction in streptozotocin-diabetic rats. J. Ethnopharmacol 2002; 81:191–197.
Gabra PH, Sirois P. Hyperalgesia in non-obese diabetic (NOD) mice: a role for the inducible bradykinin B1 receptor. Eur J Pharm 2005; 514:61–67.
Albertson C, Davis C, Ellison J, Chu C. Clinical evaluation of a new miniaturized biosensor for self-monitoring of blood glucose. Clin Chem 1998; 44:2056–2057.
Varma MVS, Panchagnula R. Enhanced oral paclitaxel absorption with vitamin E-TPGS: effect on solubility and permeability in vitro, in situ and in vivo. Eur J Pharm Sci 2005; 25:445–453.
Zhang Q, Yie G, Li Y, Yang Q, Nagai T. Studies on the cyclosporin: A loaded stearic acid nanoparticles. Int J Pharm 2000; 200:153–159.
Wagner SG. Fundamentals of Clinical Pharmacokinetics, first ed. Drug Intelligence Publications Inc., Hamilton, Illinois 1975; p.71.
Mooter GV, Augustijns P, Blaton N, Kinget R.Physico-chemical characterization of solid dispersions of temazepam with polyethylene glycol 6000 and PVP K30. Int J Pharm. 1998, 164, 67–80.
Costa P and Lobo JMS. Modeling and comparison of dissolution profiles. Eur J Pharm Sci 2001; 13:123-133.
Korsemeyer RW, Gurney R, Doelker E, Buri P, Peppas NA. Mechanisms of solute release from porous hydrophilic polymers. Int J Pharm 1983; 15:25–35.
Biswal S, Sahoo J, Murthy PN, R. Giradkar P and Avari JG. Enhancement of Dissolution Rate of Gliclazide Using Solid Dispersions with Polyethylene Glycol 6000. AAPS Pharm Sci Tech 2008;9(2):563-570.
Valizadeh H, Nokhodchi A, Qarakhani N, Zakeri-Milani P, Azarmi S, Hassanzadeh D, Lobenberg R. Physicochemical characterization of solid dispersions of indomethacin with PEG 6000, Myrj 52, Lactose, Sorbitol, Dextrin, and Eudragit E100. Drug Dev and Ind Pharm 2004; 30(3):303–317.
How to Cite
Copyright (c) 2021 soudamini Mallick
This work is licensed under a Creative Commons Attribution 4.0 International License.