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

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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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