Formulation and Characterization of Bilastine – Ternary Cyclodextrin Inclusion Complex

Authors

  • Eman B. H. Al-Khedairy Department of Pharmaceutics, College of Pharmacy, University of Baghdad, Baghdad, Iraq.
  • Sura Salam Hatam Ministry of Health, Babylon Health Directorate, Babylon, Iraq

DOI:

https://doi.org/10.31351/vol34iss1pp143-155

Keywords:

Bilastine, inclusion complex, cyclodextrins , methyl beta cyclodextrin , soluplus

Abstract

Abstract

                Bilastine (BLA)  is a modern second – generation antihistamine employed to manage symptoms associated with allergic rhinoconjuctivitis and urticaria. However, it is very slightly soluble in water with low bioavailability, which affects its therapeutic action. The main objective of this research was to enhance the solubility and dissolution rate of BLA by complexation technique using beta cyclodextrin)β-CD)  and its derivatives,  hydroxypropyl beta cyclodextrin) HP-β-CD), methyl beta cyclodextrin(M-β-CD), and sulfobutyl ether beta cyclodextrin (SBE-β- CD) . Binary and ternary complexes using different hydrophilic polymers were prepared using kneading, solvent evaporation, co-grinding, and microwave methods. The  resulting complexes were characterized for their percentage yield, drug content, solubility, and dissolution. The best complex was further characterized by XRD and FT-IR. The obtained results revealed that the ternary complex consisting of BLA, M-β CD, and soluplus ®  (1mole /1mole / 5%  w/w ) prepared by solvent evaporation method, exhibited the highest solubility (7.8 times  more than the pure BLA)  and the fastest release rate, where 90 %  of BLA was released within the first 15 minutes at pH 6.8 with percentage yield of 89.3 % and 100 % drug content. Furthermore, the FTIR analysis confirmed the inclusion of BLA within the cavity of M-β CD. Additionally, the XRD diffractograms indicated the amorphous nature of the resulting complex

How to Cite

1.
Al-Khedairy EBH, Salam Hatam S. Formulation and Characterization of Bilastine – Ternary Cyclodextrin Inclusion Complex. Iraqi Journal of Pharmaceutical Sciences [Internet]. 2025 Mar. 29 [cited 2025 Apr. 1];34(1):143-55. Available from: https://bijps.uobaghdad.edu.iq/index.php/bijps/article/view/3002

Publication Dates

Received

2023-09-24

Revised

2023-10-12

Accepted

2024-01-03

Published Online First

2024-03-29

References

Martin AN, Sinko PJ, Singh Y. Martin ‘s physical pharmacy and pharmaceutical sciences: physical chemical and biopharmaceutical principles in the pharmaceutical sciences. Wolters Kluwer; 2006.

Sadoon NA, Ghareeb MM. Formulation and characterization of isradipine as oral nanoemulsion. Iraqi J Pharm Sci 2020; 29 (1): 143-153.

Ismail M Y, Ghareeb MM. Enhancement of solubility and dissolution rate of rebamipide by using solid dispersion technique. Iraq J Pharm Sci. 2018; 27 (2): 55- 65.

Noor A D, Al-khedairy E B H. Formulation and evaluation of silymarin as microcrystal by in-situ micronization technique. Iraqi J Pharm Sci. 2019; 28 (1): 1- 16.

Savjani KT, Gajjar AK, Savjani JK. Drug solubility: importance and enhancement techniques. ISRN. 2012; 3: 1-10.

Kumar, Sandeep; Singh, Pritam. Various techniques for solubility enhancement: An overview. The Pharma Innovation, 2016, 5 (1): 23-28.

Togawa M, Yamaya H, Rodriguez M, Nagashima H. Pharmacokinetics, pharmacodynamics and population pharmacokinetic / pharmacodynamic modeling of bilastine, a second generation antihistamine, in healthy Japanese. Clin Drug Investig 2016; 6 (3): 1011-1021.

Nechipadappu SK, Swain D. Combined synthetic and solubility aspects of orotate salt of bilastine. Journal of Molecular Structure. 2023; 1271: Article 134148.

Rathi SG, Chaudhari DB, Vaghela SS, Kamani KK. Physicochemical characterization and dissolution enhancement of bilastine by solid dispersion. Int. J. Pharm. Sci. Rev. Res. 2021; 69 (1): 194- 200.

Jain H, Chella N. Methods to improve the solubility of therapeutical natural products: a review. Environmental Chemistry Letters. 2021; 19 (1) :111-121.

Kumar k S, Sushma M, Raju Y P. Dissolution enhancement of poorly soluble drugs by using complexation technique – a review. J. Pharm. Sci & Res. 2013; 5 (5): 120-124.

Muankaew C, Loftsson T. Cyclodextrin – based formulations: A non- Invasive platform for targeted drug delivery. Basic & Clinical Pharmacology & Toxicology. 2017; 122(1): 46-55

H. Qi, C. Sikorski, Controlled delivery using cyclodextrin technology. Pharm. Tech. Europe Nov. 2001; 13 (11): 17-26.

Loh G O K, Tan Y T F, Peh K K. Enhancement of norfloxacin solubility via inclusion complexation with β-cyclodextrin and its derivative hydroxyl propyl – β-cyclodextrin. Asian Journal of Pharmaceutical Sciences. 2016; (11): 536-549.

Chadha R, Arora P, Bhandari S. Effect of hydrophilic polymer on complexing efficiency of cyclodextrins towards efavirenz – characterization and thermodynamic parameters. J Incl Phenom Macrocycl Chem. 2012; (27): 275-287.

Higuchi, T.; Connors, K. A. Phase solubility techniques. Adv. Anal. Chem. Instrum. 1965; 4:117-212.

Saokham P, Muankaew C, Jansook P, Loftsson T. Solubility of cyclodextrin and drug / cyclodextrin complexes. Molecules. 2018; 23 (5): 1161.

Hussain HAM, Al-khedairy EBH. Preparation and in vitro evaluation of cyclodextrin based effervescent and dispersible granules of carbamazepine. International Journal of Applied Pharmaceutics. 2018; 10 (6): 290-297.

Ghosh A, Biswas S, Ghosh T. Preparation and evaluation of silymarin β-cyclodextrin molecular inclusion complexes. J Young Pharm 2011; 3 (3): 205-10.

Das S, Mohanty S, Maharana J, Jena SR, Nayak J, Subuddhi U. Microwave assisted β- cyclodextrin / chrysin inclusion complexation: An economical and green strategy for enhanced hemocompatibility and chemosensitivity in vitro. Journal of Molecular Liquids. 2020; 310 (6).

Kondoros BA, Laczkovich O, B erkesi O, Aigner Z. Analytical investigation of cyclodextrin complexation using the Co- Gringing technique in the case of terbinafine hydrochloride. proceedings 2021; 78 (19): 1-6.

Hadi BM, Al-khedairy EBH. Preparation and characterization of atorvastatine calcium trihydrate – cyclodextrin inclusion complex. International Journal of Drug Delivery Technology. 2022; 12 (3): 1171-1179.

Mohammed Ihsan A, Ghareeb MM. Investigation of solubility enhancement approach of ticagrelor. Iraqi J Pharm Sci . 2018; 27 (1): 8-19.

Diaz DA, Colgan ST, Langer CS, Bandi NT, Likar MD, Van Alstine L. Dissolution similarity requirements: how similar or dissimilar are the global regulatory expectations. The AAPS journal. 2016 ;18(1):15-22.

Muhesen R A, Rajab NA. Formulation and characterization of olmesartan medoxomil as a nanoparticle. Research J. Pharm. and Tech. 2023; 16 (7): 1-7.

Al-sarraf MA, Hussein AA, Al-kinani KK. Formulation, characterization, and optimization of zaltoprofen nanostructured lipid carriers. International Journal of drug delivery Technology. 2021; 11 (2): 434-442.

Gabriel O K L, Fung Tan Y T, Khiang Peh K, Enhancement of norfloxacin solubility via cyclodextrin complexation with β- cyclodextrin and its derivative hydroxypropyl-β- cyclodextrin Asian Journal of Pharmaceutical 2016; 11: 536-546.

Jagdale S. K, Dehghan M.H, Paul N. S. Enhancement of dissolution of fenofibrate using complexation with hydroxyl propyl β-cyclodextrin. Turk J Pharm Sci. 2019; 16 (1): 48-53.

Mohammed A, Singh S, Swain S. Cyclodextrins: concept to applications, requlatory issues and challenge. Nanomed Res J, 2020; 5(3): 202-214.

Miranda JCD, Martins TEA, Veiga F, Ferraz HG. Cyclodextrin and ternary complexes: technology to improve solubility of poorly soluble drugs. Brazilian Journal Pharmaceutical Sciences .2011; 47 (4): 665-681.

Lula S. I, Teixeira H, Sinisterra R, Bassani V.L. Daidzein / cyclodextrin / hydrophilic polymer ternary systems. Drug Development and Industrial Pharmacy. 2011; 37 (8): 886-893.

Munir R, Hadi A, Din khan S.U, Asghar S, Irfan M, Khan I. U, Hameed M. Solubility and dissolution enhancement of dexibuprofen with hydroxyl propyl beta cyclodextrin and poloxamers (188/407) inclusion complexes: preparation and in vitro characterization. Polymers. 2022; 14 (579): 1-21.

Aulton ME, Taylor K. Aulton’s pharmaceutics: the design and manufacture of medicines. Elsevier Health Sciences; 2013.

Mane P.T, Wakure B.S, Wakte PS. Ternary inclusion complex of docetaxel using β-cyclodextrin and hydrophilic polymer: physicochemical characterization and in – vitro anticancer activity. Journal of Applied Pharmaceutical Science. 2022; 12 (12): 150-161.

Lu N, Xu H, Liu Y. Characterization and antimicrobial activity of a 2-Omethyl-β-cyclodextrin inclusion complex containing hexahydro-β-acids. J Mater Sci. 2019; 54(1): 4287–4296.

Lin HL, Chi YT, Huang YT, Kao CY, Lin SY. DSC-FTIR Combined approaches used to simultaneously prepare/determine the amorphous solid dispersions of indomethacin/soluplus in real-time. EC Pharmaceutical Science. 2015;2(1):183-193.

Ribeiro A, Figueiras A, Santos D, Veiga F. Preparation and solid –state characterization of inclusion complexes formed between miconazole and methyl- β-cyclodextrin. AAPS Pharm Sci Tech. 2008; 9 (4): 1102-9.

Downloads

Published

2025-03-29