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Current Drug Delivery

Editor-in-Chief

ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

Research Article

Release Kinetics of Hydroxypropyl Methylcellulose Governing Drug Release and Hydrodynamic Changes of Matrix Tablet

Author(s): Chulhun Park, Jong Hoon Lee, Gang Jin, Hai Van Ngo, Jun-Bom Park, Thao T.D. Tran, Phuong H.L. Tran and Beom-Jin Lee*

Volume 19, Issue 5, 2022

Published on: 13 January, 2022

Page: [520 - 533] Pages: 14

DOI: 10.2174/1567201818666210820101549

Price: $65

Abstract

Background: Hydrophilic Hydroxypropyl Methylcellulose (HPMC) matrix tablets are the standard role model of the oral controlled-release formulation. Nevertheless, the HPMC kinetics for the mechanistic understanding of drug release and hydrodynamic behaviors are rarely investigated. This study aims to investigate the release behaviors of both HPMC and paracetamol (model drug) from the hydrophilic matrix tablet.

Methods: Two different viscosity grades of HPMC were used (Low viscosity: 6 cps, High viscosity: 4,000 cps). Three different ratios of drug/HPMC (H:38.08%, M:22.85%, and L:15.23% (w/w) of HPMC amounts in total weight) matrix tablets were prepared by wet granulation technique. The release profiles of the drug and HPMC in a matrix tablet were quantitatively analyzed by HPLC and 1H-Nuclear Magnetic Resonance (NMR) spectroscopy. The hydrodynamic changes of HPMC were determined by the gravimetric behaviors such as swelling and erosion rates, gel layer thickness, front movement data,and distributive Near-Infrared (NIR) chemical imaging of HPMC in a matrix tablet during the dissolution process.

Results: High viscosity HPMC tablets showed slower release of HPMC than the release rate of drug, suggesting that drug release preceded polymer release.Different hydration phenomenon was qualitatively identified and corresponded to the release profiles. The release behaviors of HPMC and drug in the tablet could be distinguished with the significant difference with fitted dissolution kinetics model (Low viscosity HPMC 6cps; Korsmeyer-Peppas model, High viscosity HPMC 4000cps; Hopfenberg model, Paracetamol; Weibull model) according to the weight of ingredients and types of HPMC.

Conclusion: The determination of HPMC polymer release correlating with drug release, hydrodynamic behavior, and NIR chemical imaging of HPMC can provide new insights into the drug release- modulating mechanism in the hydrophilic matrix system.

Keywords: Hydroxypropyl methylcellulose, polymer release, drug release, hydrodynamic behaviors, distributive imaging of polymer, quantitative and qualitative analysis of HPMC.

Graphical Abstract
[1]
Qiu, Y.; Chen, Y.; Zhang, G.G.Z.; Yu, L.; Mantri, R.V. Developing solid oral dosage forms: Pharmaceutical theory and practice; Academic press: USA, 2016.
[2]
Omidian, H.; Park, K. 1.131 - Superporous Hydrogels for Drug Delivery Systems. In: Comprehensive Biomaterials; Ducheyne, P., Ed.; Elsevier: Oxford, 2011, pp. 563-576.
[http://dx.doi.org/10.1016/B978-0-08-055294-1.00044-1]
[3]
Cao, Q.R.; Choi, Y.W.; Cui, J.H.; Lee, B.J. Effect of solvents on physical properties and release characteristics of monolithic hydroxypropylmethylcellulose matrix granules and tablets. Arch. Pharm. Res., 2005, 28(4), 493-501.
[http://dx.doi.org/10.1007/BF02977682] [PMID: 15918526]
[4]
Cao, Q.R.; Choi, J.S.; Liu, Y.; Xu, W.J.; Yang, M.; Lee, B.J.; Cui, J.H. A formulation approach for development of HPMC-based sustained release tablets for tolterodine tartrate with a low release variation. Drug Dev. Ind. Pharm., 2013, 39(11), 1720-1730.
[http://dx.doi.org/10.3109/03639045.2012.730528] [PMID: 23062115]
[5]
Tran, T.T.D.; Tran, P.H.L. Perspectives on strategies using swellable polymers in solid dispersions for controlled drug release. Curr. Pharm. Des., 2017, 23(11), 1639-1648.
[http://dx.doi.org/10.2174/1381612822666161021152932] [PMID: 27774901]
[6]
Dürig, T.; Karan, K. Binders in Wet Granulation. In: Handbook of Pharmaceutical Wet Granulation; Narang, A.S.; Badawy, S.I.F., Eds.; Academic Press: USA, 2019, pp. 317-349.
[7]
Park, J.B.; Lim, J.; Kang, C.Y.; Lee, B.J. Drug release-modulating mechanism of hydrophilic hydroxypropylmethylcellulose matrix tablets: Distribution of atoms and carrier and texture analysis. Curr. Drug Deliv., 2013, 10(6), 732-741.
[http://dx.doi.org/10.2174/156720181006131125155652] [PMID: 23855499]
[8]
Tran, P.H.; Choe, J.S.; Tran, T.T.; Park, Y.M.; Lee, B.J. Design and mechanism of on-off pulsed drug release using nonenteric polymeric systems via pH modulation. AAPS PharmSciTech, 2011, 12(1), 46-55.
[http://dx.doi.org/10.1208/s12249-010-9562-1] [PMID: 21161457]
[9]
Tran, P.H.; Tran, T.T.; Piao, Z.Z.; Vo, T.V.; Park, J.B.; Lim, J.; Oh, K.T.; Rhee, Y.S.; Lee, B.J. Physical properties and in vivo bioavailability in human volunteers of isradipine using controlled release matrix tablet containing self-emulsifying solid dispersion. Int. J. Pharm., 2013, 450(1-2), 79-86.
[http://dx.doi.org/10.1016/j.ijpharm.2013.04.022] [PMID: 23612354]
[10]
Hamed, R.; Al Baraghthi, T.; Sunoqrot, S. Correlation between the viscoelastic properties of the gel layer of swollen HPMC matrix tablets and their in vitro drug release. Pharm. Dev. Technol., 2018, 23(9), 838-848.
[http://dx.doi.org/10.1080/10837450.2016.1257022] [PMID: 27808590]
[11]
Kang, W.H.; Nguyen, H.V.; Park, C.; Choi, Y.W.; Lee, B.J. Modulation of microenvironmental pH for dual release and reduced in vivo gastrointestinal bleeding of aceclofenac using hydroxypropyl methylcellulose-based bilayered matrix tablet. Eur. J. Pharm. Sci., 2017, 102, 85-93.
[http://dx.doi.org/10.1016/j.ejps.2017.02.039]
[12]
Dawaba, H.M.; Dawaba, A.M. Development and evaluation of extended release ciprofloxacin HCl ocular inserts employing natural and synthetic film forming agents. J. Pharm. Investig., 2018, 49(2), 245-257.
[http://dx.doi.org/10.1007/s40005-018-0400-x]
[13]
Hardy, I.J.; Windberg-Baarup, A.; Neri, C.; Byway, P.V.; Booth, S.W.; Fitzpatrick, S. Modulation of drug release kinetics from hydroxypropyl methyl cellulose matrix tablets using polyvinyl pyrrolidone. Int. J. Pharm., 2007, 337(1-2), 246-253.
[http://dx.doi.org/10.1016/j.ijpharm.2007.01.026] [PMID: 17306477]
[14]
Lee, K-H.; Park, C.; Oh, G.; Park, J-B.; Lee, B-J. New blends of hydroxypropylmethylcellulose and Gelucire 44/14: Physical property and controlled release of drugs with different solubility. J. Pharm. Investig., 2017, 48(3), 313-321.
[http://dx.doi.org/10.1007/s40005-017-0322-z]
[15]
Krese, A.; Kovacic, N.N.; Kapele, T.; Mrhar, A.; Bogataj, M. Influence of ionic strength and HPMC viscosity grade on drug release and swelling behavior of HPMC matrix tablets. J. Appl. Polym. Sci., 2016, 133(26)
[http://dx.doi.org/10.1002/app.43604]
[16]
Eftimov, P.; Stefanova, N.; Lalchev, Z.; Georgiev, G.A. Effect of hydrophilic polymers on the wettability, static and dynamic, of solid substrate covered by confluent monolayer of air-damaged SIRC cells. Biotechnol. Biotechnol. Equip., 2015, 29(2), 390-394.
[http://dx.doi.org/10.1080/13102818.2014.997541] [PMID: 26019657]
[17]
Zhang, J.; Zhang, L.; Gong, X. Large-scale spraying fabrication of robust fluorine-free superhydrophobic coatings based on dual-sized silica particles for effective antipollution and strong buoyancy. Langmuir, 2021, 37(19), 6042-6051.
[http://dx.doi.org/10.1021/acs.langmuir.1c00706] [PMID: 33939432]
[18]
Zhong, L.; Tao, H.; Gong, X. Superhydrophobic poly(l-lactic acid) membranes with fish-scale hierarchical microstructures and their potential application in oil-water separation. Langmuir, 2021, 37(22), 6765-6775.
[http://dx.doi.org/10.1021/acs.langmuir.1c00858] [PMID: 34029095]
[19]
Wei, D.W.; Wei, H.; Gauthier, A.C.; Song, J.; Jin, Y.; Xiao, H. Superhydrophobic modification of cellulose and cotton textiles: Methodologies and applications. J. Biores. Bioproducts., 2020, 5(1), 1-15.
[http://dx.doi.org/10.1016/j.jobab.2020.03.001]
[20]
Mamani, P.L.; Ruiz-Caro, R.; Veiga, M.D. Matrix tablets: The effect of hydroxypropyl methylcellulose/anhydrous dibasic calcium phosphate ratio on the release rate of a water-soluble drug through the gastrointestinal tract I. in vitro tests. AAPS PharmSciTech, 2012, 13(4), 1073-1083.
[http://dx.doi.org/10.1208/s12249-012-9829-9] [PMID: 22907778]
[21]
Caccavo, D.; Lamberti, G.; Barba, A.A.; Abrahmsen-Alami, S.; Viriden, A.; Larsson, A. Effects of HPMC substituent pattern on water up-take, polymer and drug release: An experimental and modelling study. Int. J. Pharm., 2017, 528(1- 2), 705-713.
[22]
Avalle, P.; Pygall, S.R.; Gower, N.; Midwinter, A. The use of in situ near infrared spectroscopy to provide mechanistic insights into gel layer development in HPMC hydrophilic matrices. Eur. J. Pharm. Sci., 2011, 43(5), 400-408.
[http://dx.doi.org/10.1016/j.ejps.2011.05.013] [PMID: 21664969]
[23]
Avalle, P.; Pygall, S.R.; Pritchard, J.; Jastrzemska, A. Interrogating erosion-based drug liberation phenomena from hydrophilic matrices using near infrared (NIR) spectroscopy. Eur. J. Pharm. Sci., 2013, 48(1-2), 72-79.
[http://dx.doi.org/10.1016/j.ejps.2012.09.010] [PMID: 23059372]
[24]
Romberg, B.; Kettenes-van den Bosch, J.J.; de Vringer, T.; Storm, G.; Hennink, W.E. 1H NMR spectroscopy as a tool for determining the composition of poly(hydroxyethyl-L-asparagine)-coated liposomes. Bioconjug. Chem., 2006, 17(3), 860-864.
[http://dx.doi.org/10.1021/bc060045a] [PMID: 16704228]
[25]
Garcia-Fuentes, M.; Torres, D.; Martín-Pastor, M.; Alonso, M.J. Application of NMR spectroscopy to the characterization of PEG-stabilized lipid nanoparticles. Langmuir, 2004, 20(20), 8839-8845.
[http://dx.doi.org/10.1021/la049505j] [PMID: 15379515]
[26]
Strübing, S.; Metz, H.; Syrowatka, F.; Mäder, K. Monitoring of dissolution induced changes in film coat composition by 1H NMR spectroscopy and SEM. J. Control. Release, 2007, 119(2), 190-196.
[http://dx.doi.org/10.1016/j.jconrel.2007.03.004] [PMID: 17434640]
[27]
Palou, A.; Cruz, J.; Blanco, M.; Tomàs, J.; de Los Ríos, J.; Alcalà, M. Determination of drug, excipients and coating distribution in pharmaceutical tablets using NIR-CI. J. Pharm. Anal., 2012, 2(2), 90-97.
[http://dx.doi.org/10.1016/j.jpha.2011.11.003] [PMID: 29403727]
[28]
Novikova, A.; Markl, D.; Zeitler, J.A.; Rades, T.; Leopold, C.S. A non-destructive method for quality control of the pellet distribution within a MUPS tablet by terahertz pulsed imaging. Eur. J. Pharm. Sci., 2018, 111, 549-555.
[http://dx.doi.org/10.1016/j.ejps.2017.10.029]
[29]
Wahl, P.R.; Pucher, I.; Scheibelhofer, O.; Kerschhaggl, M.; Sacher, S.; Khinast, J.G. Continuous monitoring of API content, API distribution and crushing strength after tableting via near-infrared chemical imaging. Int. J. Pharm., 2017, 518(1- 2), 130-137.
[30]
Tung, N.T.; Nguyen, C.H.; Nguyen, V.D.; Nguyen, T.H.T.; Nguyen, V.L.; Tran, C.S.; Pham, T.M.H. Formulation and in vivo imaging evaluation of colonic targeting tablets prepared by a simple dry powder coating technique. J. Pharm. Investig., 2020, 50(4), 383-398.
[http://dx.doi.org/10.1007/s40005-019-00463-x]
[31]
Ward, A.; Walton, K.; Mawla, N.; Kaialy, W.; Liu, L.; Timmins, P.; Conway, B.R.; Asare-Addo, K. Development of a novel method utilising dissolution imaging for the measurement of swelling behaviour in hydrophilic matrices. Int. J. Pharm. X., 2019, 1, 100013.
[http://dx.doi.org/10.1016/j.ijpx.2019.100013]
[32]
Guo, Q.; Nie, L.; Li, L.; Zang, H. Estimation of the critical quality attributes for hydroxypropyl methylcellulose with near-infrared spectroscopy and chemometrics. Spectrochim Acta A Mol. Biomol. Spectrosc., 2017, 177, 158-163.
[http://dx.doi.org/10.1016/j.saa.2017.01.012]
[33]
Naiserová, M.; Kubová, K.; Vysloužil, J.; Pavloková, S.; Vetchý, D.; Urbanová, M.; Brus, J.; Vysloužil, J.; Kulich, P. Investigation of dissolution behavior HPMC/Eudragit®/magnesium aluminometasilicate oral matrices based on NMR solid-state spectroscopy and dynamic characteristics of gel layer. AAPS PharmSciTech, 2018, 19(2), 681-692.
[http://dx.doi.org/10.1208/s12249-017-0870-6] [PMID: 28971441]
[34]
Choiri, S.; Sulaiman, T.N.S.; Rohman, A. Reducing burst release effect of freely water-soluble drug incorporated into gastro-floating formulation below HPMC threshold concentration through interpolymer complex. AAPS PharmSciTech, 2019, 20(5), 196.
[http://dx.doi.org/10.1208/s12249-019-1414-z] [PMID: 31123934]
[35]
Piao, Z.Z.; Lee, K.H.; Kim, D.J.; Lee, H.G.; Lee, J.; Oh, K.T.; Lee, B.J. Comparison of release-controlling efficiency of polymeric coating materials using matrix-type casted films and diffusion-controlled coated tablet. AAPS PharmSciTech, 2010, 11(2), 630-636.
[http://dx.doi.org/10.1208/s12249-010-9377-0] [PMID: 20373152]
[36]
Draksler, P.; Janković, B.; Abramović, Z.; Lavrič, Z.; Meden, A. Assessment of critical material attributes of polyethylene oxide for formulation of prolonged-release tablets. Drug Dev. Ind. Pharm., 2019, 45(12), 1949-1958.
[http://dx.doi.org/10.1080/03639045.2019.1689991] [PMID: 31752546]
[37]
Hiremath, P.; Nuguru, K.; Agrahari, V. Material Attributes and Their Impact on Wet Granulation Process Performance. In: Handbook of Pharmaceutical Wet Granulation; Narang, A.S.; Badawy, S.I.F., Eds.; Academic Press: USA, 2019, pp. 263-315.
[http://dx.doi.org/10.1016/B978-0-12-810460-6.00012-9]
[38]
Jain, A.K.; Soderlind, E.; Viriden, A.; Schug, B.; Abrahamsson, B.; Knopke, C.; Tajarobi, F.; Blume, H.; Anschutz, M.; Welinder, A.; Richardson, S.; Nagel, S.; Abrahmsen-Alami, S.; Weitschies, W. The influence of hydroxypropyl methylcellulose (HPMC) molecular weight, concentration and effect of food on in vivo erosion behavior of HPMC matrix tablets. J. Control Release, 2014, 187, 50-58.
[39]
Nam, K.Y.; Cho, S.M.; Choi, Y.W.; Park, C.; Meghani, N.M.; Park, J.B.; Lee, B.J. Double controlled release of highly insoluble cilostazol using surfactant-driven pH dependent and pH-independent polymeric blends and in vivo bioavailability in beagle dogs. Int J Pharm, 2019, 558, 284-290.
[http://dx.doi.org/10.1016/j.ijpharm.2019.01.004]
[40]
Van Nguyen, H.; Nguyen, V.H.; Lee, B.J. Dual release and molecular mechanism of bilayered aceclofenac tablet using polymer mixture. Int. J. Pharm., 2016, 515(1-2), 233-244.
[http://dx.doi.org/10.1016/j.ijpharm.2016.10.021] [PMID: 27744034]
[41]
Mikac, U.; Sepe, A.; Gradisek, A.; Kristl, J.; Apih, T. Dynamics of water and xanthan chains in hydrogels studied by NMR relaxometry and their influence on drug release. Int. J. Pharm., 2019, 563, 373-383.
[http://dx.doi.org/10.1016/j.ijpharm.2019.04.014]
[42]
Zhang, Y.; Huo, M.; Zhou, J.; Zou, A.; Li, W.; Yao, C.; Xie, S. DDSolver: An add-in program for modeling and comparison of drug dissolution profiles. AAPS J., 2010, 12(3), 263-271.
[http://dx.doi.org/10.1208/s12248-010-9185-1] [PMID: 20373062]
[43]
Zuo, J.Y.; Park, C.; Doschak, M.; Löbenberg, R. Are the release characteristics of Erzhi pills in line with traditional Chinese medicine theory? A quantitative study. J. Integr. Med., 2021, 19(1), 50-55.
[http://dx.doi.org/10.1016/j.joim.2020.10.004] [PMID: 33162375]
[44]
Ghori, M.U.; Ginting, G.; Smith, A.M.; Conway, B.R. Simultaneous quantification of drug release and erosion from hypromellose hydrophilic matrices. Int. J. Pharm., 2014, 465(1- 2), 405-412.
[http://dx.doi.org/10.1016/j.ijpharm.2014.02.028]
[45]
Cao, Q.R.; Choi, Y.W.; Cui, J.H.; Lee, B.J. Formulation, release characteristics and bioavailability of novel monolithic hydroxypropylmethylcellulose matrix tablets containing acetaminophen. J. Control. Release, 2005, 108(2-3), 351-361.
[http://dx.doi.org/10.1016/j.jconrel.2005.08.004] [PMID: 16154656]
[46]
Mircioiu, C.; Voicu, V.; Anuta, V.; Tudose, A.; Celia, C.; Paolino, D.; Fresta, M.; Sandulovici, R.; Mircioiu, I. Mathematical modeling of release kinetics from supramolecular drug delivery systems. Pharmaceutics, 2019, 11(3), 140.
[http://dx.doi.org/10.3390/pharmaceutics11030140] [PMID: 30901930]
[47]
Lwin, W.W.; Puyathorn, N.; Senarat, S.; Mahadlek, J.; Phaechamud, T. Emerging role of polyethylene glycol on doxycycline hyclate-incorporated Eudragit RS in situ forming gel for periodontitis treatment. J. Pharm. Investig., 2019, 50(1), 81-94.
[http://dx.doi.org/10.1007/s40005-019-00430-6]
[48]
Bettini, R.; Bonferoni, M.C.; Colombo, P.; Zanelotti, L.; Caramella, C. Drug release kinetics and front movement in matrix tablets containing diltiazem or metoprolol/lambda- carrageenan complexes. Biomed. Res. Int., 2014, 2014, 671532.
[49]
Lajevardi, A.; Sadr, M.H.; Yaraki, M.T.; Badiei, A.; Armaghan, M. A pH-responsive and magnetic Fe3O4@ silica@ MIL-100 (Fe)/β-CD nanocomposite as a drug nanocarrier: Loading and release study of cephalexin. New J. Chem., 2018, 42(12), 9690-9701.
[http://dx.doi.org/10.1039/C8NJ01375F]
[50]
Akbarzadeh, I.; Yaraki, M.T.; Ahmadi, S.; Chiani, M.; Nourouzian, D. Folic acid-functionalized niosomal nanoparticles for selective dual-drug delivery into breast cancer cells: An in-vitro investigation. Adv. Powder Technol., 2020, 31(9), 4064-4071.
[http://dx.doi.org/10.1016/j.apt.2020.08.011]
[51]
Ghafelehbashi, R.; Akbarzadeh, I.; Tavakkoli Yaraki, M.; Lajevardi, A.; Fatemizadeh, M.; Heidarpoor Saremi, L. Preparation, physicochemical properties, in vitro evaluation and release behavior of cephalexin-loaded niosomes. Int. J. Pharm., 2019, 569, 118580.
[http://dx.doi.org/10.1016/j.ijpharm.2019.118580]
[52]
Akbarzadeh, I.; Yaraki, M.T.; Bourbour, M.; Noorbazargan, H.; Lajevardi, A.; Shilsar, S.M.S.; Heidari, F.; Mousavian, S.M. Optimized doxycycline-loaded niosomal formulation for treatment of infection-associated prostate cancer: An in-vitro investigation. J. Drug Deliv. Sci. Technol., 2020, 57, 101715.

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