Solubility and Dissolution Rate Enhancement of Bilastine by Solid Dispersion Technique
DOI:
https://doi.org/10.31351/vol34iss1pp218-229Keywords:
bilastine, solid dispersion technique, aqueous solubility, solvent evaporation, PVP K30Abstract
Bilastine (BLS) is non-sedating new-brand H1 antihistamine that has selective peripheral effects, the drug has a problem of an insufficient aqueous solubility and accordingly low dissolution rate, and low bioavailability. Solid dispersion (SD) is one of the most effective techniques for improving the solubility and the dissolution rate of poorly soluble drugs by the dispersion of drug within an inert hydrophilic carrier.
The aim of this study is to increase the solubility and dissolution rate of the BLS using SD technique. Twenty-nine BLS SD formulas were prepared using different carrier polymers include Pluronic 407 (Poloxamer407), Poloxamer188, Urea, Polyethylene glycol 6000 (PEG6000) and Polyvinylpyrrolidone (PVP K30) and employing two different preparation methods (solvent evaporation and kneading method) at different drug: polymer ratios (1:1 ,1:3,1:5,1:10,1:15). The prepared SD formulas were evaluated for their percent yield, drug content, aqueous solubility, dissolution rate, PXRD, and FTIR.
The SD technique successfully improved the solubility and dissolution rate of BLS. The improvement was largely dependent on the polymer type and drug: polymer ratio. The solubility improvement using different polymers was in the following order: PVP K30> PLX188> PEG6000> Urea> PLX407. The solid dispersion formula that showed the best outcomes in terms of dissolution improvement was prepared using the solvent evaporation technique employing PVP K30 at ratio of drug: polymer of 1:15. The optimized formula showed 10.2 folds increment in the solubility compared to pure BLS. It can be concluded that the SD technique can successfully improve the solubility and dissolution rate by solvent evaporation method with careful selection of the carrier polymer and drug: polymer ratio.
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References
Leceta A, García A, Sologuren A, Campo C. Bilastine 10 and 20 mg in paediatric and adult patients: an updated practical approach to treatment decisions. Drugs Context. 2021; 10:1-15.
Church MK, Tiongco-Recto M, Ridolo E, Novak Z. Bilastine: a lifetime companion for the treatment of allergies. Curr Med Res Opin. 2020; 36:445-54.
Nechipadappu, Kumar S, Swain, Debasish. Combined synthetic and solubility aspects of orotate salt of bilastine. J Mol Struct. 2023; 1271:1-4.
Bhalani DV, Nutan B, Kumar A, Singh Chandel AK. Bioavailability enhancement techniques for poorly aqueous Soluble Drugs and Therapeutics. Biomedicines. 2022; 10:171-5.
Ladan Akbarpour Nikghalb, Gurinder Singh, Gaurav Singh a, Kahkeshan KF. Solid dispersion: methods and polymers to increase the solubility of poorly soluble drugs. J Appl Pharm Sci. 2012; 2(10):170-5.
Choi JS, Lee SE, Jang WS, Byeon JC, Park JS. Solid dispersion of dutasteride using the solvent evaporation method: approaches to improve dissolution rate and oral bioavailability in rats. J Drug Deliv Sci Technol. 2018; 90:387-96.
Sadrani Dolly A, Ajay N. Talele, Anuradha P. Prajapati, Narkhede SB. Formulation developement and evaluation of sublingual drug delivery system of bilastine for allergic rhinoconjunctivitis Indo American journal of pharmaceutical sciences. 2021;08(04):166-81.
Slámová M, Školáková T, Školáková A, Patera J, Zámostný P. Preparation of solid dispersions with respect to the dissolution rate of active substance. J Drug Deliv Sci Technol. 2020; 56:1-9.
S.H. S, S.B. S, A.S. K, N.H. A. Solid dispersion: a novel approach for poorly water soluble drugs. Int J Curr Pharm Res. 2015; 7:1-8.
Malkawi R, Malkawi WI, Al-Mahmoud Y, Tawalbeh J. Current trends on solid dispersions: past, present, and future. Adv Pharmacol Pharm Sci. 2022; 2022:1-17.
Shamsuddin, Fazil M, Ansari SH, Ali J. Development and evaluation of solid dispersion of spironolactone using fusion method. Int J Pharm Investig. 2016; 6(1):63-8.
Mohylyuk V, Pauly T, Dobrovolnyi O, Scott N, Jones DS, Andrews GP. Effect of carrier type and Tween® 80 concentration on the release of silymarin from amorphous solid dispersions. J Drug Deliv Sci Technol. 2021; 63:102416.
Raj AL, Kumar YS. Preparation and evaluation of solid dispersion of nebivolol using solvent evaporation method. International Journal of Pharmaceutical Sciences and Drug Research. 2018;10(4).
Chhater S, Praveen K. Solvent evaporation method for amorphous solid dispersions: predictive tools for improve the dissolution rate of pioglitazone hydrochloride. International Journal of Pharmaceutical, Chemical and Biological Sciences. 2013; 3(2):350-9.
Mustapha M.AlKhalidi, Jawad FJ. Enhancement of aqueous solubility and dissolution rate of etoricoxib by solid dispersion technique. Iraqi J Pharm Sci. 2020;29(1):76-87.
Jassim BM, Al-Khedairy EBH. Enhancement of silymarin solubility and dissolution by nicotinamide-based solid dispersion employing the kneading method. J Popul Ther Clin Pharmacol. 2023; 30:e286-e93.
Ghareeb MM, Abdulrasool AA, Hussein AA, Noordin MI. Kneading technique for preparation of binary solid dispersion of meloxicam with poloxamer 188. AAPS PharmSciTech. 2009;10(4):1206-15.
Ismail MY, M. Ghareeb M. Enhancement of the solubility and dissolution rate of rebamipide by using solid dispersion technique (part I). Iraqi J Pharm Sci. 2018:55-65.
B. H. Al-Khedairy, Eman Alhassani, Radhi H. Formulation and in-vitro evaluation of meloxicam solid dispersion using natural polymers. Iraqi J Pharm Sci. 2021;30(1):169-78.
Ali SK, B. H. Al-Khedairy E. Solubility and dissolution enhancement of atorvastatin calcium using solid dispersion adsorbate technique. Iraqi J Pharm Sci. 2019; 28:105-14.
Kandukuri Rekha, Aruna, Rinku Mathappan, Mekkanti Manasa Rekha, Karthik S. Formulation and development of bilastine tablets 20mg. World J Pharm Res. 2019; 8:2197-224.
Ahmad A. E. Alezzy, Eman B. H. Al-Khedairy. Preparation and evaluation of aceclofenac solid dispersion by fusion technique and effervescent assisted fusion technique: comparative study. Research J Pharm and Tech. 2023; 16(11):5358-65.
Areej Wahhab Alhagiesa, M. Ghareeb M. Formulation and characterization of nimodipine nanoparticles for the enhancement of solubility and dissolution rate. Iraqi J Pharm Sci. 2021; 30:143-52.
Al-Khedairy EBH, Hussein LS. Solubility and dissolution enhancement of ebastine by surface solid dispersion technique. Iraqi J Pharm Sci. 2021; 30:122-32.
Sareen S, Joseph L, Mathew G. Improvement in solubility of poor water-soluble drugs by solid dispersion. Int J Pharm Investig. 2012; 2:12-7.
Alshehri S, Imam SS, Hussain A, Altamimi MA, Alruwaili NK, Alotaibi F, et al. Potential of solid dispersions to enhance solubility, bioavailability, and therapeutic efficacy of poorly water-soluble drugs: newer formulation techniques, current marketed scenario and patents. Drug Deliv. 2020; 27:1625-43.
Shan X, Moghul MA, Williams AC, Khutoryanskiy VV. Mutual effects of hydrogen bonding and polymer hydrophobicity on ibuprofen crystal inhibition in solid dispersions with poly (N-vinyl pyrrolidone) and poly(2-oxazolines). Pharmaceutics. 2021; 13:1-18.
Liw JJ, Teoh X-Y, Teoh AXY, Chan S-Y. The effect of carrier-drug ratios on dissolution performances of poorly soluble drug in crystalline solid dispersion system. JPharmaSci. 2022; 111:95-101.
Konno H, Handa T, Alonzo DE, Taylor LS. Effect of polymer type on the dissolution profile of amorphous solid dispersions containing felodipine. Eur J Pharm Biopharm. 2008; 70:493-9.
Zahraa Kareem Hussein, Al-Kinani KK. Formulation and evaluation of the risperidone solid dispersion using different carriers. J Res Med Dent Sci. 2023; 7:26-34.
Priyanka Shrestha, Shiva Kumar Bhandari, SM Ashraful Islam aSA. Dissolution enhancement of glimepiride by solid dispersion technique. Res J Pharm Biol Chem Sc. 2014; 5:977-90.
Nair AR, Lakshman YD, Anand VSK, Sree KSN, Bhat K, Dengale SJ. Overview of extensively employed polymeric carriers in solid dispersion technology. AAPS PharmSciTech. 2020; 21:1-20.
Kurakula M, Rao G. Pharmaceutical assessment of polyvinylpyrrolidone (PVP): as excipient from conventional to controlled delivery systems with a spotlight on covid-19 inhibition. J Drug Deliv Sci Technol. 2020; 60:102046.
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. 2018; 18:15-22.
Yadav PS, Kumar V, Singh UP, Bhat HR, Mazumder B. Physicochemical characterization and in vitro dissolution studies of solid dispersions of ketoprofen with PVP K30 and d-mannitol. Saudi Pharm J. 2013; 21(1):77-84.
Abbas IK, Abddulhameed SN. Preparation and characterization of bilastine solid self-nanoemulsion using liquisolid technique. Al-Rafidain Journal of Medical Sciences 2023; 5:78-85.
Yadav PS, Kumar V, Singh UP, Bhat HR, Mazumder B. Physicochemical characterization and in vitro dissolution studies of solid dispersions of ketoprofen with pvp k30 and d-mannitol. Saudi Pharm J. 2013; 21:77-84.
Shavi GV, Kumar AR, Usha YN, Armugam K, Ranjan Op, Ginjupalli K, et al. Enhanced dissolution and bioavailability of gliclazide using solid dispersion techniques. International Journal of Drug Delivery. 2010; 2:49-57.
Vaishnavi Ladhake, Samiksha Kadu, Vaishnavi Tayade, Shweta Gawande, Malviya V. Preparation and evaluation of oral fast dissolving films of bilastine using pullulan. International Journal of Scientific Development and Research. 2020; 5:282-7.
Dahash RA, A. Rajab N. Formulation and investigation of lacidipine as a nanoemulsions. Iraqi J Pharm Sci. 2020; 29:41-54.
Rosiak N, Wdowiak K, Tykarska E, Cielecka-Piontek J. Amorphous solid dispersion of hesperidin with polymer excipients for enhanced apparent solubility as a more effective approach to the treatment of civilization diseases. Int J Mol Sci. 2022; 23:1-20.
Kazi M, Al-Qarni H, Alanazi FK. Development of oral solid self-emulsifying lipid formulations of risperidone with improved in vitro dissolution and digestion. Eur J Pharm Biopharm. 2017; 114:239-49.
Del Río Pericacho JL, Puigjaner Vallet MC, Lopez RP, Yolanda Esther Arredondo Martinez YE. Crystalline forms of bilastine and preparation methods thereof. European Patent Application (EP 3 327 012 A1). 2018.
Alman, Ardiansyah, Ellyza Nasrul, Harrizul Rivai, Elfi Sahlan Ben, Zaini E. Physicochemical characterization of amorphous solid dispersion of ketoprofen–polyvinylpyrrolidone k-30. Int J Pharm Pharm Sci. 2014; 7:209-12.
Liu P, Zhou JY, Chang JH, Liu XG, Xue HF, Wang RX, et al. Soluplus-mediated diosgenin amorphous solid dispersion with high solubility and high stability: development, characterization and oral bioavailability. Drug Des Devel Ther. 2020; 14:2959-75.
Iyer R, Petrovska Jovanovska V, Berginc K, Jaklic M, Fabiani F, Harlacher C, et al. Amorphous solid dispersions (Asd): the influence of material properties, manufacturing processes and analytical technologies in drug product development. Pharmaceutics. 2021; 13:1-41.
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