Enhanced dissolution and solubility of Epalrestat with β-Cyclodextrin ternary complex using Arginine
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.
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.
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (SeeÂ The Effect of Open Access).