DEVELOPMENT OF AMORPHOUS BINARY AND TERNARY SOLID DISPERSIONS OF NATEGLINIDE FOR IMPROVED SOLUBILITY AND DISSOLUTION
Keywords:Nateglinide, Solid dispersion, Dissolution, Solubility enhancement
Objective: Nateglinide is a commonly used oral hypoglycemic, biopharmaceutical classification system Class II drug, which shows relatively poor water solubility and variable bioavailability. The objective of the present investigation was to develop the binary and ternary solid dispersions of nateglinide for improved solubility and dissolution.
Methods: Nateglinide solid dispersions were prepared by a common solvent evaporation method. Polymers like soluplus, kolliphor P188, sylloid 244FP, gelucire 48/16, affinisol (HPMCAS), HPβCD, βCD were used in different combinations. The physicochemical characterization of the optimized ternary dispersion was studied by using FT-IR, DSC, and PXRD. Solubility and dissolution behavior of all dispersions were studied.
Result: From all prepared ternary solid dispersions, nateglinide dissolution was significantly faster than pure nateglinide. With ternary solid dispersion of NTG, soluplus and kolliphor P188 there was a big improvement in solubility and dissolution. This combination enhanced the solubility of NTG by 23 folds. Another ternary dispersion of NTG with soluplus and gelucire 48/16 enhanced solubility by 25 fold.
Conclusion: Ternary solid dispersion found superior over binary dispersions. For the ternary dispersions, showing the best solubility, tablets were prepared. Dissolution and drug release from the formulated tablet was as good as a marketed product.
Zhang X, Xing H, Zhao Y, Zhiguo Ma. Pharmaceutical dispersion techniques for dissolution and bioavailability enhancement of poorly water-soluble drugs. Pharmaceutics 2018;10:74.
Deng L, Wang Y, Gong T, Sun X, Zhang ZR. Dissolution and bioavailability enhancement of alpha-Asarone by solid dispersions via oral administration. Drug Dev Ind Pharm 2017;43:1817-26.
Mokale V, Naik J, Patil K, Chaudhari R, Khairnar G. Enhancement of solubility with the formulation and in vitro evaluation of oral nateglinide compacts by liquisolid technique. Adv Diabetes Metab 2013;1:57-64.
Sahoo RK, Biswas N, Guha A, Sahoo N, Kuotsu K. Development and in vitro/in vivo evaluation of controlled release provesicles of a nateglinide–maltodextrin complex. Acta Pharm Sinica B 2014;4:408-16.
Wairkara S, Gauda R, Jadhav N. Enhanced dissolution and bioavailability of Nateglinide by microenvironmental pH-regulated ternary solid dispersion: in vitro and in vivo evaluation. J Pharm Pharmacol 2017;69:1099-109.
Campbell IW. Nateglinide–current and future role in the treatment of patients with type 2 diabetes mellitus. Int J Clin Pract 2005;59:1218-28.
Suvarna V, Kajwe A, Murahari M, Pujar GV, Inturi BK, Sherje AP. Inclusion complexes of nateglinide with HP–β–CD and L-arginine for solubility and dissolution enhancement: preparation, characterization, and molecular docking study. J Pharm Innovation 2017;12:168-81.
Singh J, Mittal P, Bonde GV, Ajmal G, Mishra B. Design, optimization, characterization and in vivo evaluation of quercetin enveloped soluplus®/P407 micelles in diabetes treatment. Artificial Cells Nanomed Biotech 2018;46:S546-S555.
Shamma RN, Basha M. Soluplus®: a novel polymeric solubilizer for optimization of carvedilol solid dispersions: formulation design and effect of method of preparation. Powder Technol 2013;237:406-14.
Miranda J, Miranda JC, Martins TEA, Veiga F, Ferraz HG. Cyclodextrins and ternary complexes: technology to improve solubility of poorly soluble drugs. Braz J Pharm Sci 2011;47:665-81.
Sherje AP, Jadhav M. β-Cyclodextrin-based inclusion complexes and nanocomposites of rivaroxaban for solubility enhancement. J Materials Sci: Materials Med 2018;29:186.
Charan K, Panigrahi C, Patra N, Jena GK, Ghose D, Jena J, et al. Gelucire: a versatile polymer for modified release drug delivery system. Future J Pharm Sci 2018;4:102-8.
Tran P, Pyo YC, Kim DH, Lee SE, Kim JK, Pars JS. Overview of the manufacturing methods of solid dispersion technology for improving the solubility of poorly water-soluble drugs and application to anticancer drugs. Pharmaceutics 2019;11:132.
Maggia L, Brunib G, Maiettab M, Canobbioa A, Cardinic A, Contea U. Technological approaches to improve the dissolution behavior of nateglinide, a lipophilic insoluble drug: nanoparticles and co-mixing. Int J Pharm 2013;454:562-7.
Mayyas AR, Ahmed MA, Ahmed K, Mohammad H. Meloxicam-paracetamol binary solid dispersion systems with enhanced solubility and dissolution rate: preparation, characterization, and in vivo evaluation. J Pharm Innov 2017;12:206-15.
Vojinovic T, Medarevic D, Vranic E, Potpara Z, Krstic M, Djuris J, et al. Development of ternary solid dispersions with hydrophilic polymer and surface adsorbent for improving the dissolution rate of carbamazepine. Saudi Pharm J 2018;26:725-32.
Nagpal N, Kaur P, Kumar R, Rahar S, Dhawan R, Arora M. Pharmaceutical diluents and their unwanted effects: a review. Bull Pharm Res 2016;6:45-9.
Nanaki S, Eleftheriou RM, Barmpalexis P, Kostoglou M, Karavas E, Bikiaris D. Evaluation of dissolution enhancement of aprepitant drug in ternary pharmaceutical solid dispersions with soluplus® and poloxamer 188 prepared by melt mixing. Science 2019;1:11.
Kunam V, Garikapati DR, Suryadevara V, Mandava VBR, Janga RB, Sunkara SP, et al. Solubility and dissolution rate enhancement of telmisartan by solid dispersion and pelletization techniques using soluplus as carrier. Int J Appl Pharm 2019;12:50-8.