Modified release of furosemide from Eudragits® and poly(ethylene oxide)-based matrices and dry-coated tablets

Marilena Vlachou 1 , Efthymia Geraniou 1  and Angeliki Siamidi 1
  • 1 Section of Pharmaceutical Technology, Department of Pharmacy


Modified release of furosemide from tablet formulations is preferred by patients, because of physiological problems, acute diuresis being the most serious, compared to the forms designed for immediate release. With this in view, we aimed at achieving furosemide’s longer gastric retention and waste minimization by preparing matrix and compression coated tablets incorporating different grades of Eudragit® and poly(ethylene oxide) (PEO), polyvinylpyrrolidone (PVP) and lactose monohydrate. Dissolution profiles of the new formulations were compared with that of the main stream drug Lasix®, 40 mg tablets. The results indicate that the use of Eudragit® in conjunction with either PVP or lactose monohydrate led to a slower release rate in the intestinal fluids compared to Lasix®. Moreover, furosemide release in the intestinal pH from matrix tablets and compression coated tablets was not noticeably different. Formulations incorporating PEO led to sustained release, in intestinal fluids, which depended on the molecular weight of PEO.

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  • 1. X. Huang, E. Dorhout Mees, P. Vos, S. Hamza and B. Braam, Everything we always wanted to know about furosemide but were afraid to ask, Am. J. Physiol.-Ren. Physiol. 310 (2016) 958–971;

  • 2. S. Kumar and M. A. Kumar, Preformulation study of furosemide, Der Pharmacia Lettre 8 (2016) 214–222.

  • 3. G. Pacifici, Clinical pharmacology of furosemide in neonates: A review, Pharmaceuticals 6 (2013) 1094–1129;

  • 4. S. W. Oh and S. Y. Han, Loop diuretics in clinical practice, Electrolytes Blood Press. 13 (2015) 17–21;

  • 5. S. Strauch, E. Jantratid, J. B. Dressman, H. E. Junginger, S. Kopp, K. K. Midha, V. P. Shah, S. Stavchansky and D. M. Barends. Biowaiver monographs for immediate release solid oral dosage forms: mefloquine hydrochloride, J. Pharm. Sci, 99 (2010) 2544–2556;

  • 6. M. Vlachou and G. Papaïoannou, Preparation and characterization of the inclusion complex of furosemide with hydroxypropyl-b-cyclodextrin, J. Biomater. Appl. 17 (2003) 197–206;

  • 7. A. Deshmukh, P. Nakhat and P. Yeole, Formulation and in-vitro evaluation of self microemulsifying drug delivery system (SMEDDS) of furosemide, Der Pharmacia Lettre 2 (2010) 94–106.

  • 8. S. Sambaraj, D. Ammula and V. Nagabandi, Furosemide loaded silica-lipid hybrid microparticles: Formulation development, in vitro and ex vivo evaluation, Adv. Pharm. Bull. 5 (2015) 403–409.

  • 9. N. J. Clear, A. Milton, M. Humphrey, B. T. Henry, M. Wulff, D. J. Nichols, R. J. Anziano and I. Wilding, Evaluation of the Intelisite capsule to deliver theophylline and frusemide tablets to the small intestine and colon, Eur. J. Pharm. Sci. 13 (2001) 375–384.

  • 10. L. Å. Brodin, Τ. Jogestrand, F. Larsen, G. Walldius and B. Tedner, Effects of furosemide and slow-release furosemide on thoracic fluid volumes, Clin. Cardiol. 9 (1986) 561–564;

  • 11. Μ. Efentakis, A. Koutlis and M. Vlachou, Development and evaluation of oral multiple-unit and single-unit hydrophilic controlled-release systems, AAPS Pharm. Sci. Tech. 1 (2000) 62–70;

  • 12. D. Jain, S. Verma, S. B. Shukla, A. K. Jain, P. Jain, P. Yadav, Formulation and evaluation of gastro-retentive tablets of Furosemide (Evaluation based on drug release kinetics and factorial designs), J. Chem. Pharm. Res. 2 (2010) 935–978.

  • 13. T. Terao, K. Matsuda and H. Shouji, Improvement in site-specifc intestinal absorption of furosemide by Eudragit L100-55, JPP 53 (2001) 433–440.

  • 14. J. M. Aceves, R. Cruz and E. Hernandez, Preparation and characterization of furosemide-eudragit controlled release systems, Int. J. Pharm. 195 (2000) 45–53;

  • 15. M. Vlachou, A. Siamidi, S. Konstantinidou and Y. Dotsikas, Optimization of controlled release matrix formulation of melatonin via experimental design, JPDDR 5 (2016) 1–5;

  • 16. M. Vlachou, A. Siamidi and M. Efentakis, Investigation of a novel “tablets in capsule” theophyl-line formulation system for modified release, Pharm. Pharmacol. Int. J. 5 (2017) 51–56;

  • 17. M. Vlachou, A. Siamidi, E. Diamantidi, A. Iliopoulou, I. Papanastasiou, V. Ioannidou, V. Kourbeli, A.-S. Foscolos, A. Vocat, S. T. Colec, V. Karalis, T. Kellici and T. Mavromoustakos, In vitro controlled release from solid pharmaceutical formulations of two new adamantane aminoethers with antitubercular activity (I) Drug Res. 67 (2017) 447–450;

  • 18. M. Vlachou, A. Siamidi, D. Spaneas, D. Lentzos, P. Ladia, K. Anastasiou, I. Papanastasiou, A-S. Foscolos, M-O. Georgiadis, V. Karalis, T. Kellici and T. Mavromoustakos, In vitro controlled release of two new tuberculocidal adamantane aminoethers from solid pharmaceutical formulations (II) Drug Res. 67 (2017) 653–660;

  • 19. M. Vlachou, M. Papamichael, A. Siamidi, I. Fragouli, P. A. Afroudakis, R. Kompogennitaki and Y. Dotsikas, Comparative in vitro controlled release studies on the chronobiotic hormone melatonin from cyclodextrins-containing matrices and cyclodextrin: Melatonin complexes, Int. J. Mol. Sci. 18 (2017) 1641;

  • 20. M. Vlachou, K.Tragou, A. Siamidi, S. Kikionis, A. L. Chatzianagnostou, A. Mitsopoulos, E. Ioannou, V. Roussis and A. Tsotinis, Modified in vitro release of the chronobiotic hormone melatonin from matrix tablets based on the marine sulfated polysaccharide ulvan, J. Drug Deliv. Sci. Technol. 44 (2018) 41–48;

  • 21. M. Vlachou, S. Kikionis, A. Siamidi, K. Tragou, S. Kapoti, E. Ioannou, V. Roussis and A. Tsotinis. Fabrication and characterization of electrospun nanofibers for the modified release of the chronobiotic hormone melatonin, Curr. Drug Deliv. 16 (2019) 79–85;

  • 22. S. Bose and R. H. Bogner, Solventless pharmaceutical coating processes: A review, Pharm. Dev. Techn. 12 (2007) 115–131;

  • 23. M. Efentakis and M. Vlachou, Evaluation of high molecular weight poly(oxyethylene) (polyox) polymer: Studies of flow properties and release rates of furosemide and captopril from controlled-release hard gelatin capsules, Pharm. Dev. Technol. 5 (2000) 339–346;

  • 24. O. Mansour, G. Ismail, M. Isbera and M. Almouhammad, Assessment of physicochemical properties of furosemide (40 mg) tablets marketed in Syria, JCPS 9 (2016) 2879–2881.

  • 25.

  • 26. K.A. Khan, The concept of dissolution efficiency, J. Pharm. Pharmacol. 27 (1975) 48–49;

  • 27. W. R. Korsmeyer, R. Gurny, E. Doelker, P. Buri and N. A. Peppas, Mechanisms of solute release from porous hydrophilic polymers, Int. J. Pharmaceut. 15 (1983) 25–35;

  • 28. N. A. Peppas and J. J. Sahlin, A simple equation for the description of solute release coupling of diffusion and relaxation, Int. J. Pharmaceut. 57 (1989) 169–172;

  • 29. G. Singhvi and M. Singh, Review: in-vitro drug release characterization models, Int. J. Pharm. Sci. Res. 2 (2011) 77–84.

  • 30. S. Ummadi, B. Shravani, N. G. Raghavendra Rao, S. Reddy, B. Sanjeev, Overview on controlled release dosage form, Int. J. Pharm. Sci. 3 (2013) 258–269;

  • 31. S. Bose and R. H. Bogner, Solventless pharmaceutical coating processes: A review, Pharm. Dev. Technol. 12 (2007) 115–131

  • 32. X. Gong, C.C. Sun, A new tablet brittleness index, Eur. J. Pharm. Biopharm. 93 (2015) 260–266;

  • 33. M. Han, Q. Yu, X. Liu, F. Hu and H. Yuan, Preparation and characterization of a novel aqueous dispersion for enteric coating of pantoprazole sodium pellets, Acta Pharm. 68 (2018) 441–455;

  • 34. J. Akbuga, Preparation and evaluation of controlled release furosemide microspheres by spherical crystallization, Int. J. Pharm. 53 (1999) 99–105;

  • 35. B. N.Tukaram, I. V. Rajagopalan and P. S. Ikumar Shartchandra, The effects of lactose, microcrystalline cellulose and dicalcium phosphate on swelling and erosion of compressed hpmc matrix tablets: texture analyzer, Iranian J. Pharm. Res. 9 (2010) 349–358.

  • 36. V. Iannuccelli, G. Coppi, E. Leo, F. Fontana and M. T. Bernabei, PVP solid dispersions for the controlled release of furosemide from a floating multiple-unit system, Drug Dev. Ind. Pharm. 26 (2000) 595–603.

  • 37. A. Cismesia, G. R. Nicholls and N. C. Polfer, Amine vs. carboxylic acid protonation in ortho-, meta-, and para aminobenzoic acid: An IRMPD spectroscopy study, J. Mol. Spectrosc. 332 (2017) 79–85;

  • 38. A. Apicella, B. Cappello, M. A. Del Nobile, M. I. La Rotonda, G. Mensitieria and L. Nicolais, Poly(ethylene oxide) (PEO) and different molecular weight PEO blends monolithic devices for drug release, Biomaterials 14 (1993) 83–90;


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