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Release Adjustment of Two Drugs with Different Solubility Combined in a Matrix Tablet

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Abstract

The objective of this study was to modify the release of two drugs having different solubility in a combined matrix tablet as a fixed-dose combination for extended release. Propranolol HCl (freely soluble) and carbamazepine (very slightly soluble) were used as model drugs, water-soluble hydroxypropyl methylcellulose (HPMC) and water-insoluble ethylcellulose (EC) were used as matrix-forming polymers. Tablets were prepared by direct compression of powder blends, or propranolol HCl was first granulated with one of the matrix-forming polymers (1:1) followed by compression with carbamazepine and matrix former. Propranolol HCl release from directly compressed tablets was faster than carbamazepine because of its higher solubility. The release of both drugs was fast when HPMC-propranolol HCl granules were compressed with carbamazepine into EC matrix tablet. Conversely, the release of both drugs was decreased when HPMC-propranolol HCl granules and carbamazepine were compressed into HPMC matrices. The desired release of both drugs was approached when EC-propranolol HCl granules were compressed with carbamazepine into HPMC matrix. Erosion of the HPMC matrix and, therefore, drug release were adjusted by varying the molecular weight of HPMC. A burst release of propranolol HCl decreased when it was granulated with EC in a fluidized bed coater followed by compression with carbamazepine into HPMC matrix.

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References

  1. Gradman AH, Basile JN, Carter BL, Bakris GL, Materson BJ, Black HR, et al. Combination therapy in hypertension. J Am Soc Hypertens. 2010;4:90–8.

    Article  CAS  Google Scholar 

  2. Reynolds JK. Fixed-dose combination of sitagliptin and metformin for the treatment of type 2 diabetes. Diabetes Metab Syndr Obes Dove Press. 2009;2:127–34.

    Article  CAS  Google Scholar 

  3. Curatolo M, Sveticic G. Drug combinations in pain treatment: a review of the published evidence and a method for finding the optimal combination. Best Pract Res Clin Anaesthesiol. 2002;16:507–19.

    Article  CAS  Google Scholar 

  4. Albanna AS, Smith BM, Cowan D, Menzies D. Fixed-dose combination antituberculosis therapy: a systematic review and meta-analysis. Eur Respir J. 2013;42:721–32.

    Article  CAS  Google Scholar 

  5. Tallarida RJ. An overview of drug combination analysis with isobolograms. J Pharmacol Exp Ther. 2006;319:1–7.

    Article  CAS  Google Scholar 

  6. Saeidipour F, Mansourpour Z, Mortazavian E, Rafiee-Tehrani N, Rafiee-Tehrani M. New comprehensive mathematical model for HPMC-MCC based matrices to design oral controlled release systems. Eur J Pharm Biopharm. 2017;121:61–72.

    Article  CAS  Google Scholar 

  7. Cai X, Luan Y, Dong Q, Shao W, Li Z, Zhao Z. Sustained release of 5-fluorouracil by incorporation into sodium carboxymethylcellulose sub-micron fibers. Int J Pharm. 2011;419:240–6.

    Article  CAS  Google Scholar 

  8. Tapia-Albarran M, Villafuerte-Robles L. Assay of amoxicillin sustained release from matrix tablets containing different proportions of Carbopol 971P NF. Int J Pharm. 2004;273:121–7.

    Article  CAS  Google Scholar 

  9. Casettari L, Bonacucina G, Cespi M, Perinelli DR, Micheli M, Cacciatore I, et al. Effect of manufacturing temperature and molecular weights on compression, mechanical and dissolution properties of PEO matrix tablets. J Drug Deliv Sci Technol Elsevier. 2016;32:236–40.

    Article  CAS  Google Scholar 

  10. Lazzari A, Kleinebudde P, Knop K. Xanthan gum as a rate-controlling polymer for the development of alcohol resistant matrix tablets and mini-tablets. Int J Pharm. 2018;536:440–9.

    Article  CAS  Google Scholar 

  11. Song SH, Chae BR, Il SS, Yeom DW, Son HY, Kim JH, et al. Formulation of controlled-release pelubiprofen tablet using Kollidon ® SR. Int J Pharm. 2016;511:864–75.

    Article  CAS  Google Scholar 

  12. Ali R. Ammonio methacrylate copolymer as a carrier for water-insoluble drug, preparation and characterization of an oral controlled-release matrix tablet. J Drug Deliv Sci Technol. 2017;41:7–12.

    Article  CAS  Google Scholar 

  13. Katikaneni PR, Upadrashta SM, Neau SH, Mitra AK. Ethylcellulose matrix controlled release tablets of a water-soluble drug. Int J Pharm Elsevier. 1995;123:119–25.

    Article  CAS  Google Scholar 

  14. Tahara K, Yamamoto K, Nishihata T. Overall mechanism behind matrix sustained release (SR) tablets prepared with hydroxypropyl methylcellulose 2910. J Control Release. 1995;35:59–66.

    Article  CAS  Google Scholar 

  15. Zuleger S, Lippold BC. Polymer particle erosion controlling drug release. I. Factors influencing drug release and characterization of the release mechanism. Int J Pharm. 2001;217:139–52.

    Article  CAS  Google Scholar 

  16. Maderuelo C, Zarzuelo A, Lanao JM. Critical factors in the release of drugs from sustained release hydrophilic matrices. J Control Release. 2011;154:2–19.

    Article  CAS  Google Scholar 

  17. Viridén A, Larsson A, Wittgren B. The effect of substitution pattern of HPMC on polymer release from matrix tablets. Int J Pharm. 2010;389:147–56.

    Article  Google Scholar 

  18. Gao P, Skoug JW, Nixon PR, Ju TR, Stemm NL, Sung KC. Swelling of hydroxypropyl methylcellulose matrix tablets. 2. Mechanistic study of the influence of formulation variables on matrix performance and drug release. J Pharm Sci. 1996;85:732–40.

    Article  CAS  Google Scholar 

  19. Viridén A, Abrahmsén-Alami S, Wittgren B, Larsson A. Release of theophylline and carbamazepine from matrix tablets – consequences of HPMC chemical heterogeneity. Eur J Pharm Biopharm. 2011;78:470–9.

    Article  Google Scholar 

  20. Viridén A, Wittgren B, Larsson A. The consequence of the chemical composition of HPMC in matrix tablets on the release behaviour of model drug substances having different solubility. Eur J Pharm Biopharm. 2011;77:99–110.

    Article  Google Scholar 

  21. Zuleger S, Fassihi R, Lippold BC. Polymer particle erosion controlling drug release. II. Swelling investigations to clarify the release mechanism. Int J Pharm. 2002;247:23–37.

    Article  CAS  Google Scholar 

  22. Grund J, Koerber M, Walther M, Bodmeier R. The effect of polymer properties on direct compression and drug release from water-insoluble controlled release matrix tablets. Int J Pharm. 2014;469:94–101.

    Article  CAS  Google Scholar 

  23. Hiremath PS, Saha RN. Oral matrix tablet formulations for concomitant controlled release of anti-tubercular drugs: design and in vitro evaluations. Int J Pharm. 2008;362:118–25.

    Article  CAS  Google Scholar 

  24. Neau SH, Howard MA, Claudius JS, Howard DR. The effect of the aqueous solubility of xanthine derivatives on the release mechanism from ethylcellulose matrix tablets. Int J Pharm. 1999;179:97–105.

    Article  CAS  Google Scholar 

  25. Siepmann F, Karrout Y, Gehrke M, Penz FK, Siepmann J. Limited drug solubility can be decisive even for freely soluble drugs in highly swollen matrix tablets. Int J Pharm. 2017;526:280–90.

    Article  CAS  Google Scholar 

  26. Badshah A, Subhan F, Rauf K. Controlled release matrix tablets of olanzapine: influence of polymers on the in vitro release and bioavailability. AAPS PharmSciTech. 2010;11:1397–404.

    Article  CAS  Google Scholar 

  27. Li L, Li J, Si S, Wang L, Shi C, Sun Y, et al. Effect of formulation variables on in vitro release of a water-soluble drug from chitosan–sodium alginate matrix tablets. Asian J Pharm Sci Elsevier. 2015;10:314–21.

    Article  Google Scholar 

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Authors and Affiliations

  1. College of Pharmacy, Freie Universität Berlin, Kelchstrasse 31, 12169, Berlin, Germany

    Anis Y. Chaerunisaa, Rebaz Ali & Andriy Dashevskiy

  2. Faculty of Pharmacy, Padjadjaran University Sumedang, Jl. Raya Jatinangor Km 21,5, Sumedang, 45363, Indonesia

    Anis Y. Chaerunisaa

  3. College of Pharmacy, University of Sulaimani, City Center Campus, Sulaimani, Kurdistan Region, Iraq

    Rebaz Ali

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  1. Anis Y. Chaerunisaa
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  2. Rebaz Ali
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Correspondence to Andriy Dashevskiy.

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Chaerunisaa, A.Y., Ali, R. & Dashevskiy, A. Release Adjustment of Two Drugs with Different Solubility Combined in a Matrix Tablet. AAPS PharmSciTech 20, 142 (2019). https://doi.org/10.1208/s12249-019-1294-2

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