Characterization, formulation and evaluation of glibenclamide with ß-cyclodextrin inclusion complexes tablets

Yandi Syukri, Farida Ulfa, Asih Lestari, Lelita Ayu Saputri, Rochmy Istikharah, Aris Perdana Kusuma


Background: Glibenclamide is an oral antidiabetic drug which is practically insoluble in water. Formation of ß-cyclodextrin inclusion complex was able to increase glibenclamide solubility. 

Objective: Aims of this study are to characterize, formulate and evaluate  inclusion complex tablets of glibenclamide to meet the requirements in Pharmacopeia.

Methods: Inclusion complex was prepared in a 1: 1 and 1: 2 molar ratio  by spray drying method. Characterization were performed by using Fourier Transform Infrared (FTIR) spectroscopy and Scanning Electron Microscope (SEM). Further, it was formulated into tablets by direct compression technique using primojel and crospovidone as disintegrants.   Uniformity weight, hardness, friability, disintegration, and tablets were evaluated include dissolution. Dissolution studies of inclusion complex were performed by using United States Pharmacopeia (USP) II apparatus.  Drug concentration dissolution was determined with high pressure liquid chromatography (HPLC).

Results: Result of FTIR and SEM provided evidence of  glibenclamide and ß-cyclodextrin complex formation after using spray drying methods. The tablet evaluation with primojel and crospovidone as disintegrant showed that increase concentration of disintegrant would increase disintegration time of the tablets. All of the formulas meet the requirements in the Pharmacopoeia.

Conclusion: The inclusion complex of glibenclamide–ß cyclodextrin successfully used for enhancing the solubility of glibenclamide. The tablets meet the requirements in Pharmacopeia.


Glibenclamide; ß-cyclodextrin; primogel; crospovidone; inclusion complex

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Elkordy AA, Jatto A, Essa E. In situ controlled crystallization as a tool to improve the dissolution of Glibenclamide. International Journal of Pharmaceutics. 2012 ;428(1–2):118–20. DOI: 10.1016/j.ijpharm.2012.02.046

Kawabata Y, Wada K, Nakatani M, Yamada S, Onoue S. Formulation design for poorly water-soluble drugs based on biopharmaceutics classification system: Basic approaches and practical applications. International Journal of Pharmaceutics. 2011 ;420(1):1–10.DOI: 10.1016/j.ijpharm.2011.08.032

Khadka P, Ro J, Kim H, Kim I, Kim JT, Kim H, et al. Pharmaceutical particle technologies: An approach to improve drug solubility, dissolution and bioavailability. Asian Journal of Pharmaceutical Science. 2014 ;9(6):304–16.DOI:

Shanmuga Priya A, Sivakamavalli J, Vaseeharan B, Stalin T. Improvement on dissolution rate of inclusion complex of Rifabutin drug with ß-cyclodextrin. International Journal Biological Macromolecules. 2013 ;62:472–80.DOI:10.1016/j.ijbiomac.2013.09.006

Taupitz T, Dressman JB, Buchanan CM, Klein S. Cyclodextrin-water soluble polymer ternary complexes enhance the solubility and dissolution behaviour of poorly soluble drugs. Case example: Itraconazole. European Journalof Pharmacetics and Biopharmaceutics. 2013 ;83(3):378–87.DOI: 10.1016/j.ejpb.2012.11.003

Michel D, Chitanda JM, Balogh R, Yang P, Singh J, Das U, et al. Design and evaluation of cyclodextrin-based delivery systems to incorporate poorly soluble curcumin analogs for the treatment of melanoma. European Journal of Pharmaceutics and Biopharmaceutics. 2012 ;81(3):548–56.DOI: 10.1016/j.ejpb.2012.03.016

Liu M, Cao W, Sun Y, He Z. Preparation, characterization and in vivo evaluation of formulation of repaglinide with hydroxypropyl-ß-cyclodextrin. International Journal of Pharmaceutics. 2014;477(1–2):159–66. DOI: 10.1016/j.ijpharm.2014.10.038

Yao Y, Xie Y, Hong C, Li G, Shen H, Ji G. Development of a myricetin/hydroxypropyl-ß-cyclodextrin inclusion complex: Preparation, characterization, and evaluation. Carbohydrate Polymers. 2014;110:329–37.DOI: 10.1016/j.carbpol.2014.04.006

Syukri Y, Fernenda L, Utami FR, Qiftayati I, Kusuma AP, Istikaharah R. Preperation and Characterization of ?-Cyclodextrin Inclusion Complexes Oral Tablets Containing Poorly Water Soluble Glimipiride Using Freeze Drying Method. Indonesian Journal of Pharmacy. 2015 ;26(2):71.DOI:

Mihajlovic T, Kachrimanis K, Graovac A, Djuric Z, Ibric S. Improvement of Aripiprazole Solubility by Complexation with (2-Hydroxy)propyl-ß-cyclodextrin Using Spray Drying Technique. AAPS PharmSciTech. 2012 ;13(2):623–31.DOI: 10.1208/s12249-012-9786-3

Borghetti GS, Lula IS, Sinisterra RD, Bassani VL. Quercetin/ß-Cyclodextrin Solid Complexes Prepared in Aqueous Solution Followed by Spray-drying or by Physical Mixture. AAPS PharmSciTech. 2009;10(1):235–42.DOI: 10.1208/s12249-009-9196-3

Rudrangi SRS, Bhomia R, Trivedi V, Vine GJ, Mitchell JC, Alexander BD, et al. Influence of the preparation method on the physicochemical properties of indomethacin and methyl-ß-cyclodextrin complexes. International Journal of Pharmaceutics. 2015 ;479(2):381–90.DOI:10.1016/j.ijpharm.2015.01.010

Cabral-Marques H, Almeida R. Optimisation of spray-drying process variables for dry powder inhalation (DPI) formulations of corticosteroid/cyclodextrin inclusion complexes. European Journal of Pharmaceutics and Biopharmaceutics. 2009;73(1):121–9.DOI: 10.1016/j.ejpb.2009.05.002

Shakeel F, Haq N, Alanazi FK, Alsarra IA. Polymeric solid self-nanoemulsifying drug delivery system of glibenclamide using coffee husk as a low cost biosorbent. Powder Technology. 2014;256:352–60.DOI: 10.1016/j.powtec.2014.02.028

Bachhav YG, Patravale VB. SMEDDS of Glyburide: Formulation, In Vitro Evaluation, and Stability Studies. AAPS PharmSciTech. 2009;10(2):482–7.DOI: 10.1208/s12249-009-9234-1

Anonymous. Farmakope Indonesia. IV. Jakarta: Ministry of Health Republic of Indonesia; 1995.

United States Pharmacopeial Convention. U.S. Pharmacopeia National Formulary. Rockville, USA: United States Pharmacopeial; 2014. (621) 1-7 (1225) 1-5. (USP 37 NF 32).

Anonymous. Farmakope Indonesia. V. Jakarta: Ministry of Health Republic of Indonesia; 2014.

Zaman MK, Arayne MS, Sultana N, FAROOQ A. Synthesis and characterization of glibenclamide complexes of magnesium, chromium, cobalt, nickel, zinc and cadmium salts. Pakistan Journal of Pharmeutical Sciences. 2006;19(2):114–118. PMID: 16751121

Roy A, Saha S, Roy MN. Exploration of inclusion complexes of probenecid with a and ß-cyclodextrins: Enhancing the utility of the drug. Journal of Molecular Structure. 2017;1144:103–11. DOI:10.1016/j.molstruc.2017.05.002

Barman BK, Barman S, Roy MN. Inclusion complexation between tetrabutylphosphonium methanesulfonate as guest and a- and ß-cyclodextrin as hosts investigated by physicochemical methodology. Journal Molecular Liquids. 2018;264:80–7. DOI: 10.1016/j.molliq.2018.04.148

Dou S, Ouyang Q, You K, Qian J, Tao N. An inclusion complex of thymol into ß -cyclodextrin and its antifungal activity against Geotrichum citri-aurantii. Postharvest Biology and Technology. 2018;138:31–6.DOI : 10.1016/j.postharvbio.2017.12.011

Desai S, Poddar A, Sawant K. Formulation of cyclodextrin inclusion complex-based orally disintegrating tablet of eslicarbazepine acetate for improved oral bioavailability. Material Science and Engineering C. 2016;58:826–34.DOI: 10.1016/j.msec.2015.09.019

Goodwin DJ, van den Ban S, Denham M, Barylski I. Real time release testing of tablet content and content uniformity. International Journal of Pharmaceutics. 2018 ;537(1–2):183–92.DOI: 10.1016/j.ijpharm.2017.12.011

Anonim. British Pharmacopeia. United Kingdom: The Stationery Office; 2625-2626 p.