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Current Drug Delivery

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

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Research Article

Preparation and Evaluation of Ternary Polymeric Blends for Controlled Release Matrices Containing Weakly Basic Model Drug

Author(s): Wasfy M. Obeidat*, Shadi F. Gharaibeh, Abdolelah A. Jaradat and Osama Abualsuod

Volume 18, Issue 1, 2021

Published on: 31 July, 2020

Page: [54 - 64] Pages: 11

DOI: 10.2174/1567201817666200731170040

Price: $65

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Abstract

Objective: The objective of this study was to evaluate the suitability of a ternary mixture of smart polymers comprised of Eudragit®E100, Eudragit®L100, and sodium alginate to serve as a carrier for sustained drug release for weakly basic drugs. The model drug chosen in this part of the study is Metronidazole.

Methods: Matrix tablet formulations were prepared by either direct compression or by wet granulation. Dissolution studies were conducted using USP XXΠ rotating paddle apparatus in three different consecutive stages (pH 1.2, 4.8, and 6.8). Tablets made of low to intermediate proportions of sodium alginate and approximately equal proportions of Eudragit®E100 and Eudragit®L100 were found to have a significant modification of drug release rates.

Results: Thus, indicating a potential for controlling the drug release for 12 hours depending on polymers ratios in the formulation. The ratio of sodium alginate to total Eudragit® polymers and the ratio of Eudragit®E100 to Eudragit®L100 within the ternary polymeric composition were found critical in determining the controlled release performance.

Conclusion: Results of swelling studies were in agreement with the dissolution behaviors of the tablets. The findings suggest the significance of the ternary polymeric compositions in controlling the release of a weakly basic drug, Metronidazole.

Keywords: Metronidazole, eudragit, sodium alginate, controlled/sustained-release, matrices, pH Profile.

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[1]
Banker, G.S.; Anderson, N.R. The theory and practice of industrial pharmacy. 3rd Ed; Lachman, L.; Lieberman, H.A.; Kanig, J.L., Eds.; Lea & Febiger: Philadelphia, 1986, pp. 293-345.
[2]
Shargel, L.; Wu Pong, S.; Yu, A. Applied biopharmaceutics & pharmacokinetics 7e. Acess Pharmacy; McGraw-Hill: New York, 2005, pp. 20-450.
[3]
Hofmann, F.F.; Pressman, J.H.; Code, C.F.F.W.K. Controlled entry of orally administered drugs: physiological consideration. Drug Dev. Ind. Pharm., 1983, 9(7), 1077-1109.
[http://dx.doi.org/10.3109/03639048309046314]
[4]
Vergnaud, J.M. Controlled drug release from oral dosage forms.Ed. Ellis Horwood Limited: London, Taylor & Francis Group, 1993, pp.426..
[http://dx.doi.org/10.1201/9781482267358]
[5]
Lordi, N. Sustained release dosage forms.The theory and practice of industrial pharmacy. 3rd Ed; Lachman, L.; Lieberman, H.A.; Kanig, J.L., Eds.; Lea and Febiger: Philadelphia, 1986, pp. 430-478..
[6]
Rao, V.M.; Engh, K.; Qiu, Y. Design of pH-independent controlled release matrix tablets for acidic drugs. Int. J. Pharm., 2003, 252(1-2), 81-86.
[http://dx.doi.org/10.1016/S0378-5173(02)00622-1] [PMID: 12550783]
[7]
Obeidat, W.M.; Abu Znait, A.H.; Sallam, A.S. Novel combination of anionic and cationic polymethacrylate polymers for sustained release tablet preparation. Drug Dev. Ind. Pharm., 2008, 34(6), 650-660.
[http://dx.doi.org/10.1080/03639040701836578] [PMID: 18568916]
[8]
Al-Zoubi, N.M.; AlKhatib, H.S.; Obeidat, W.M. Evaluation of hydrophilic matrix tablets based on Carbopol(®) 971P and low-viscosity sodium alginate for pH-independent controlled drug release. Drug Dev. Ind. Pharm., 2011, 37(7), 798-808.
[http://dx.doi.org/10.3109/03639045.2010.545068] [PMID: 21247372]
[9]
Obeidat, W.M.; Nokhodchi, A.; Alkhatib, H. Evaluation of matrix tablets based on eudragit®E100/Carbopol®971P combinations for controlled release and improved compaction properties of water soluble model drug paracetamol. AAPS PharmSciTech, 2015, 16(5), 1169-1179.
[http://dx.doi.org/10.1208/s12249-015-0301-5] [PMID: 25724162]
[10]
Bhanudas, S.K.; Sanjay, P.B. Preformulation and formulation studies of novel pH independent controlled release drug delivery system of quetiapine fumarate. J. Pharm. Res., 2009, 2(1), 110-119.
[11]
Li, L.; Wang, L.; Shao, Y.; Ni, R.; Zhang, T.; Mao, S. Drug release characteristics from chitosan-alginate matrix tablets based on the theory of self-assembled film. Int. J. Pharm., 2013, 450(1-2), 197-207.
[http://dx.doi.org/10.1016/j.ijpharm.2013.04.052]
[12]
Mandal, S.; Basu, S.K.; Sa, B. Sustained release of a water-soluble drug from alginate matrix tablets prepared by wet granulation method. AAPS PharmSciTech, 2009, 10(4), 1348-1356.
[http://dx.doi.org/10.1208/s12249-009-9333-z] [PMID: 19911286]
[13]
Yusif, R.M.; Abu Hashim, I.I.; El-Dahan, M.S. Some variables affecting the characteristics of Eudragit E-sodium alginate polyelectrolyte complex as a tablet matrix for diltiazem hydrochloride. Acta Pharm., 2014, 64(1), 89-104.
[http://dx.doi.org/10.2478/acph-2014-0010] [PMID: 24670354]
[14]
Streubel, A.; Siepmann, J.; Dashevsky, A.; Bodmeier, R. pH-independent release of a weakly basic drug from water-insoluble and -soluble matrix tablets. J. Control. Release, 2000, 67(1), 101-110.
[15]
AlKhatib, H.S.; Aiedeh, K.M.; Bustanji, Y.; Hamed, S.; Mohammad, M.K.; AlKhalidi, B. Modulation of buspirone HCl release from hypromellose matrices using chitosan succinate: implications for pH-independent release. Eur. J. Pharm. Biopharm., 2008, 70(3), 804-812.
[16]
Korber, M.; Ciper, M.; Hoffart, V.; Pearnchob, N.; Walther, M.; Macrae, R.J. Enteric polymers as acidifiers for the pH-independent sustained delivery of a weakly basic drug salt from coated pellets., European J. Pharmaceut. Biopharmaceut., : Official J. Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik eV, 2011, 78(3), 447-54..
[http://dx.doi.org/10.1016/j.ejpb.2011.03.018]
[17]
Moustafine, R.I.; Bukhovets, A.V.; Sitenkov, A.Y.; Kemenova, V.A.; Rombaut, P.; Van den Mooter, G. Eudragit E PO as a complementary material for designing oral drug delivery systems with controlled release properties: comparative evaluation of new interpolyelectrolyte complexes with countercharged eudragit L100 copolymers. Mol. Pharm., 2013, 10(7), 2630-2641.
[http://dx.doi.org/10.1021/mp4000635] [PMID: 23777284]
[18]
Löfmark, S.; Edlund, C.; Nord, C.E. Metronidazole is still the drug of choice for treatment of anaerobic infections. Clin. Infect. Dis., 2010, 50(Suppl. 1), S16-S23.
[http://dx.doi.org/10.1086/647939] [PMID: 20067388]
[19]
Özyazıcı, M.; Gökçe, E.H.; Ertan, G. Release and diffusional modeling of metronidazole lipid matrices. Eur. J. Pharm. Biopharm., 2006, 63(3), 331-339.
[20]
Sriamornsak, P.; Thirawong, N.; Korkerd, K. Swelling, erosion and release behavior of alginate-based matrix tablets. Eur. J. Pharm. Biopharm., 2007, 66(3), 435-450.
[http://dx.doi.org/10.1016/j.ejpb.2006.12.003]
[21]
Chen, T.; Chen, L.; Li, H.; Chen, Y.; Guo, H.; Shu, Y. Design and in vitro evaluation of a novel poly(methacrylic acid)/metronidazole antibacterial nanogel as an oral dosage form. Colloids Surf. B Biointerfaces, 2014, 118, 65-71.
[22]
Singh, R.; Maity, S.; Sa, B. Effect of ionic crosslink on the release of metronidazole from partially carboxymethylated guar gum tablet. Carbohydr. Polym., 2014, 106, 414-421.
[http://dx.doi.org/10.1016/j.carbpol.2014.01.033]
[23]
McGinity, J.W. Aqueous polymeric coatings for pharmaceutical dosage forms. Ed: McGinity, J.W.; 2nd Ed; Dekker M.; New York, 1997, pp. 101-176..
[24]
Nakano, Y.; Maeda, A.; Uchida, S.; Namiki, N. Preparation and evaluation of unpleasant taste-masked pioglitazone orally disintegrating tablets. Int. J. Pharm., 2013, 446(1-2), 160-165.
[http://dx.doi.org/10.1016/j.ijpharm.2013.02.019] [PMID: 23419665]
[25]
Tan, Q.; Zhang, L.; Liu, G.; He, D.; Yin, H.; Wang, H.; Wu, J.; Liao, H.; Zhang, J. Novel taste-masked orally disintegrating tablets for a highly soluble drug with an extremely bitter taste: design rationale and evaluation. Drug Dev. Ind. Pharm., 2013, 39(9), 1364-1371.
[http://dx.doi.org/10.3109/03639045.2012.718784] [PMID: 22994163]
[26]
Jijun, F.; Lishuang, X.; Xiaoli, W.; Shu, Z.; Xiaoguang, T.; Xingna, Z.; Haibing, H.; Xing, T. Nimodipine (NM) tablets with high dissolution containing NM solid dispersions prepared by hot-melt extrusion. Drug Dev. Ind. Pharm., 2011, 37(8), 934-944.
[http://dx.doi.org/10.3109/03639045.2010.550301] [PMID: 21417606]
[27]
Kabanova, T.V.; Mustafine, R.I. Synthesis and characterization of an interpolyelectrolyte complex based on Eudragit E100 and L100 copolymers. Pharm. Chem. J., 2004, 38(11), 625-627.
[http://dx.doi.org/10.1007/s11094-005-0044-9]
[28]
Moustafine, R.I.; Bobyleva, O.V. Design of new polymer carriers based of Eudragit E PO/Eudragit L100-55 interpolyelectrolyte complexes using swellability measurements. J. Controlled Release Soc., 2006, 116(2), e35-e36.
[29]
Leopold, C.S. Coated dosage forms for colon-specific drug delivery. Pharm. Sci. Technol. Today, 1999, 2(5), 197-204.
[http://dx.doi.org/10.1016/S1461-5347(99)00151-0]
[30]
Di Colo, G.; Falchi, S.; Zambito, Y. In vitro evaluation of a system for pH-controlled peroral delivery of metformin. J. Controlled Release Soc., 2002, 80(1-3), 119-128.
[http://dx.doi.org/10.1016/S0168-3659(02)00022-6]
[31]
Alvarez-Fuentes, J.; Fernández-Arévalo, M.; González-Rodríguez, M.L.; Cirri, M.; Mura, P. Development of enteric-coated timed-release matrix tablets for colon targeting. J. Drug Target., 2004, 12(9-10), 607-612.
[http://dx.doi.org/10.1080/10611860400013501] [PMID: 15621686]
[32]
Sharma, P.; Chawla, A.; Pawar, P. Design, development, and optimization of polymeric based-colonic drug delivery system of naproxen. Sci World J, 2013, 2013654829
[http://dx.doi.org/10.1155/2013/654829] [PMID: 24198725]
[33]
Varum, FJ; Hatton, GB; Freire, AC; Basit, A.W. A novel coating concept for ileo-colonic drug targeting: proof of concept in humans using scintigraphy., European J. Pharmaceut. Biopharmaceut., : official J. Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik eV, 2013, 84(3), 573-7..
[http://dx.doi.org/10.1016/j.ejpb.2013.01.002 ]
[34]
Chaudhary, S.S.; Patel, H.K.; Parejiya, P.B.; Shelat, P.K. Chronomodulated drug delivery system of urapidil for the treatment of hypertension. Int. J. Pharm. Investig., 2015, 5(2), 107-113.
[http://dx.doi.org/10.4103/2230-973X.153389] [PMID: 25838996]
[35]
Liew, C.V.; Chan, L.W.; Ching, A.L.; Heng, P.W.S. Evaluation of sodium alginate as drug release modifier in matrix tablets. Int. J. Pharm., 2006, 309, 25-37.
[http://dx.doi.org/10.1016/j.ijpharm.2005.10.040]
[36]
Efentakis, M.; Buckton, G. The effect of erosion and swelling on the dissolution of theophylline from low and high viscosity sodium alginate matrices. Pharm. Dev. Technol., 2002, 7(1), 69-77.
[http://dx.doi.org/10.1081/PDT-120002232] [PMID: 11852698]
[37]
Tønnesen, H.H.; Karlsen, J. Alginate in drug delivery systems. Drug Dev. Ind. Pharm., 2002, 28(6), 621-630.
[http://dx.doi.org/10.1081/DDC-120003853] [PMID: 12149954]
[38]
Costa, P; Sousa Lobo, J.M. Modeling and comparison of dissolution profiles. European J. Pharmaceut. Sci., 2001, 13(2), 123-33..
[http://dx.doi.org/10.1016/S0928-0987(01)00095-1]
[39]
Wu, Y.; Fassihi, R. Stability of metronidazole, tetracycline HCl and famotidine alone and in combination. Int. J. Pharm., 2005, 290(1-2), 1-13.
[http://dx.doi.org/10.1016/j.ijpharm.2004.10.015] [PMID: 15664125]
[40]
Yalkowsky, S.H.; Yan, H. An extensive compilation of aqueous solubility data for organic compounds extracted from the aquasol database. Handbook Aqueous Solubil. Data, 1st ed; CRC Press LLC: Boca Raton, 2003, p. 1512.
[http://dx.doi.org/10.1201/9780203490396]
[41]
Kibbe, A.H. Handbook of pharmaceutical excipients, 3rd Ed; Washington, D.C, Am. Pharmaceut.Associat., 2000, pp. 665..
[42]
Obeidat, W.M.; Abuznait, A.H.; Sallam, A.S. Sustained release tablets containing soluble polymethacrylates: comparison with tableted polymethacrylate IPEC polymers. AAPS PharmSciTech, 2010, 11(1), 54-63.
[http://dx.doi.org/10.1208/s12249-009-9348-5] [PMID: 20054671]
[43]
Moustafine, R.I.; Kemenova, V.A.; Van den Mooter, G. Characteristics of interpolyelectrolyte complexes of Eudragit E 100 with sodium alginate. Int. J. Pharm., 2005, 294(1-2), 113-120.
[http://dx.doi.org/10.1016/j.ijpharm.2005.01.029] [PMID: 15814235]
[44]
Olorunsola, E.O.; Akpan, G.A.; Adikwu, M.U. Evaluation of chitosan-microcrystalline cellulose blends as direct compression excipients. J. Drug Deliv., 2017, 20178563858
[http://dx.doi.org/10.1155/2017/8563858] [PMID: 29410919]
[45]
Vasvári, G.; Haimhoffer, Á.; Horváth, L.; Budai, I.; Trencsényi, G.; Béresová, M.; Dobó-Nagy, C.; Váradi, J.; Bácskay, I.; Ujhelyi, Z.; Fehér, P.; Sinka, D.; Vecsernyés, M.; Fenyvesi, F. Development and characterisation of gastroretentive solid dosage form based on melt foaming. AAPS PharmSciTech, 2019, 20(7), 290.
[http://dx.doi.org/10.1208/s12249-019-1500-2] [PMID: 31428895]
[46]
Loh, Z.C.; Elkordy, A.A. Formulation and evaluation of different floating tablets containing metronidazole to target stomach. Curr. Drug Deliv., 2015, 12(4), 425-443.
[http://dx.doi.org/10.2174/156720181204150729125655] [PMID: 25924732]
[47]
Bani-Jaber, A.; Al-Aani, L.; Alkhatib, H.; Al-Khalidi, B. Prolonged intragastric drug delivery mediated by Eudragit® E-carrageenan polyelectrolyte matrix tablets. AAPS PharmSciTech, 2011, 12(1), 354-361.
[http://dx.doi.org/10.1208/s12249-011-9595-0] [PMID: 21302009]
[48]
Moustafine, R.I.; Zaharov, I.M.; Kemenova, V.A. Physicochemical characterization and drug release properties of Eudragit E PO/Eudragits L 100-55 interpolyelectrolyte complexes European J. Pharmaceut. Biopharmaceut., 2006, 63(1), 26-36.

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