Enhanced dissolution and solubility of Epalrestat with β-Cyclodextrin ternary complex using Arginine

  • Sneha Jagtap Annasaheb Dange College of B Pharmacy, Ashta, Sangli - 416301 Maharashtra, India.
  • Magdum Chandrakant Rajarambapu College of Pharmacy, Kasegaon, Sangli -415404 Maharashtra, India.


The objective of present is work to achieve improvement in solubility and dissolution using Epalrestat with β-cyclodextrin ternary complex with addition of L-arginine. Kneading method with and without incorporation of L-arginine was used to obtain the solid systems (binary and ternary complex) of Epalrestat with β-cyclodextrin and characterized for DSC, PXRD, SEM. Phase solubility, saturation solubility, dissolution and stability studies were carried out. The effect of L-arginine was investigated on complexation efficiency of β-cyclodextrin towards Epalrestat in an aqueous media through phase solubility according to Higuchi and Connors. Phase solubility studies showed AL (linear) type of solubility curve in presence of L-arginine, the complexation efficiency and association constant of β-cyclodextrin towards Epalrestat were promoted by L-arginine signifying its use as a ternary component. Dissolution rate of Epalrestat and solubility were significantly improved by complexation with β-cyclodextrin as compared to Epalrestat alone. Ternary complex incorporated with L-arginine proved better than binary complex. Hence, L-arginine could be exploited as a ternary component to improve the solubility of Epalrestat via β-cyclodextrin complexation.

Keywords: Epalrestat, solubility enhancement, inclusion complexes, β-cyclodextrin, L-arginine.


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Author Biographies

Sneha Jagtap, Annasaheb Dange College of B Pharmacy, Ashta, Sangli - 416301 Maharashtra, India.

Annasaheb Dange College of B Pharmacy, Ashta, Sangli - 416301 Maharashtra, India.

Magdum Chandrakant, Rajarambapu College of Pharmacy, Kasegaon, Sangli -415404 Maharashtra, India.

Rajarambapu College of Pharmacy, Kasegaon, Sangli -415404 Maharashtra, India.


1. Takayuki F, Shoma T, Noriko O, Mihoko G, Enhanced dissolution and skin permeation profiles of epalrestat with β-cyclodextrin derivatives using a cogrinding method, Eur J Pharm Sci, 2017; 106:79-86.
2. Callaghan BC, Cheng HT, Stables CL, Smith AL, Feldman EL, Diabetic neuropathy: clinical manifestations and current treatments, Lancet Neurol, 2012; 11:521–534.
3. Ramirez MA, Borja NL, Epalrestat: an aldose reductase inhibitor for the treatment of diabetic neuropathy, Pharmacotherapy, 2008; 28:646–655.
4. Ohmura C, Watada H, Azuma K, Shimizu T, Kanazawa A, Ikeda F, Yoshihara T, et al, Aldose reductase inhibitor, epalrestat, reduces lipid hydroperoxides in type 2 diabetes, Endocr, J 2009; 56:149–156.
5. Oates PJ, Mylari BL, Aldose reductase inhibitors: therapeutic implications for diabetic complications, Expert Opin Investig Drugs, 1999; 8:2095–2119.
6. Brewster ME, Loftsson T, Cyclodextrins as pharmaceutical solubilizers, Adv Drug Deliv Rev, 2007; 59:645–666.
7. Loftsson T, Duchene D, Cyclodextrins and their pharmaceutical applications, Int J Pharm, 2007; 329:1–11.
8. Mohammed J, Ashok M, Mohammed IK, Ameliorated solubility and dissolution rate of glimepiride by cyclodextrin ternary complexes employing amino acids, Int J Pharm Sci Res, 2017; 8(6):2443-2451.
9. Sapte S, Pore Y, Inclusion complexes of cefuroxime axetil with βcyclodextrin: Physicochemical characterization, molecular modeling and effect of l-arginine on Complexation, J Pharm Anal, 2016; 6:300-306.
10. Valero M, Perez-Revuelta BI, Rodriguez LJ, Effect of PVP K-25 on the formation of the naproxen: β-cyclodextrin complex, Int J Pharm, 2003; 253:97-110.
11. Gajare P, Patil C, Kalyane N, Effect of hydrophilic polymer on pioglitazone complexation with hydroxyl propyl b-cyclodextrin, Dig J Nanomater Bios, 2009; 4:891-897.
12. El-Maradny HA, Mortada SA, Kamel OA, Hikal AH, Characterization of ternary complexes of meloxicam-HPβ-CD and PVP or L-arginine prepared by the spray-drying technique, Acta Pharm, 2008; 58:455–466.
13. Bramhane DM, Saindane NS, Vavia PR, Inclusion complexation of weakly acidic NSAID with b-cyclodextrin: selection of arginine, an amino acid, as a novel ternary component, J. Incl. Phenom, Macrocycl. Chem 2011; 69:453–460.
14. Maheshwari DG, Chaudhari Kl, Development and Validation of UV Spectrophotometric Method for Simultaneous estimation of Epalrestat and Methylcobalamin in the Pharmaceutical Dosage Form, Int J Pharmtech Res, 2014; 6(4):1180-1188.
15. Higuchi T, Connors KA, Phase-solubility techniques, Adv Anal Chem Instr, 1965; 4:117-212.
16. Jadhav P, Pore Y, Physiochemical Thermodynamic and analytical studies on binary and ternary inclusion complex of bosentan with hydroxyl – B-cyclodextrin, Bulletin of Faculty of Pharmacy Cairo University, 2017; 55:147-154.
17. Sherje AP, Kulkarni V, Murahari M, Nayak UY, Bhat P, Suvarna V, et al, Inclusion Complexation of Etodolac with Hydroxypropyl-betacyclodextrin and Auxiliary Agents: Formulation Characterization and Molecular Modeling Studies, Mol Pharm, 2017; 3:14(4):1231-1242.
18. Ribeiro L, Loftsson T, Ferreira D, Investigation and physicochemical characterization of vinpocetine-sulfobutyl ether b -cyclodextrin binary and ternary complexes. Chem Pharm Bull 2003; 51:914-922.
19. Patil A, Pore Y, Kuchekar B, Effect of L-arginine on bicalutamide complexation with hydroxypropyl-b-cyclodextrin, Dig J Nanomater Bios, 2008; 3:89-98.
20. Jadhav P, Pethkar B, Pore Y, Physicochemical and molecular modeling studies of cefixime-L-arginine-cyclodextrin ternary inclusion compounds, Carbohydr Polym, 2013; 98:1317-1325.
21. Fernandes CM, Vieira MT, Veiga FJ, Physicochemical characterization and in vitro dissolution behavior of nicardipine–cyclodextrins inclusion compounds, Eur J Pharm, 2002; 15(1):79-88.
22. Shinde VR, Shelake MR, Shetty SS, Enhanced solubility and dissolution rate of lamotrigine by inclusion complexation and solid dispersion technique, J Pharm Pharmacol, 2008; 60:1121-1129.
23. Laveneziana D, Speranzam R, Raullim P, Ibuprofen – arginine in the management of pain, Clin Drug Invest, 1996; 11:1-7.
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Jagtap S, Chandrakant M. Enhanced dissolution and solubility of Epalrestat with β-Cyclodextrin ternary complex using Arginine. JDDT [Internet]. 15Nov.2018 [cited 30Nov.2020];8(6):62-7. Available from: http://jddtonline.info/index.php/jddt/article/view/2014