Generic placeholder image

Current Drug Delivery


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

Research Article

Utilization of a Single Experimental Design for the Optimization of Furosemide Modified-Release Tablet Formulations

Author(s): Marilena Vlachou*, Angeliki Siamidi and Yannis Dotsikas

Volume 16, Issue 10, 2019

Page: [931 - 939] Pages: 9

DOI: 10.2174/1567201816666191029130324

Price: $65


Background: The loop diuretic drug furosemide is widely used for the treatment of edema in various conditions, such as pulmonary, cardiac and hepatic edema, as well as cardiac infarction. Furosemide, due to its poor water solubility and low bioavailability after oral administration of conventional dosage form, is categorized as class IV in the biopharmaceutical classification system.

Objective: In the case of furosemide, this release profile is responsible for various physiological problems, acute diuresis being the most serious. This adverse effect can be circumvented by the modified release of furosemide from tablet formulations compared to those forms designed for immediate release.

Methods: In this report, a D-optimal combined experimental design was applied for the development of furosemide containing bilayer and compression coated tablets, aiming at lowering the drug’s burst release in the acidic environment of the stomach. A D-optimal combined design was selected in order to include all requirements in one design with many levels for the factors examined. The following responses were selected as the ones reflecting better criteria for the desired drug release: dissolution at 120 min (30-40%), 300 min (60-70%) and 480 min >95%. The new formulations, suggested by the Doptimal combined design, incorporated different grades of Eudragit ® polymers (Eudragit® E100 and Eudragit® L100-55), lactose monohydrate and HPMC K15M. The dissolution profile of furosemide from these systems was probed via in vitro dissolution experiments in buffer solutions simulating the pH of the gastrointestinal tract.

Results: The results indicate that the use of Eudragit® E100 in conjunction with lactose monohydrate led to 21.32-40.85 % drug release, in the gastric medium, in both compression-coated and bilayer tablets. This is lower than the release of the mainstream drug Lasix® (t=120 min, 44.5% drug release), implying longer gastric retention and drug waste minimization.

Conclusion: Furosemide’s release in the intestinal environment, from compression coated tablets incorporating Eudragit® L100-55 and HPMC K15M in the inner core or one of the two layers of the bilayer tablets, was delayed, compared to Lasix®.

Keywords: D-optimal experimental design, compression-coated tablets, bilayer systems, furosemide modified release, biopharmaceutical classification system, acute diuresis.

Graphical Abstract
Huang, X.; Dorhout Mees, E.; Vos, P.; Hamza, S.; Braam, B. Everything we always wanted to know about furosemide but were afraid to ask. Am. J. Physiol. Ren Physiol., 2016, 310, 958-971.
Kumar, S.; Kumar, M.A. Preformulation study of furosemide. Der Pharmacia Lettre, 2016, 8, 214-222.
[] [PMID: 30965943]
Pacifici, G.M. Clinical pharmacology of furosemide in neonates: A review. Pharmaceuticals (Basel), 2013, 6(9), 1094-1129.
[] [PMID: 24276421]
Oh, S.W.; Han, S.Y. Loop diuretics in clinical practice. Electrolyte Blood Press., 2015, 13(1), 17-21.
[] [PMID: 26240596]
Patel, R.C.; Keraliya, R.A.; Patel, M.M.; Patel, N.M. Formulation of furosemide solid dispersion with micro crystalline cellulose for achieve rapid dissolution. J. Adv. Pharm. Technol. Res., 2010, 1(2), 180-189.
[PMID: 22247844]
Terao, T.; Matsuda, K.; Shouji, H. Improvement in site-specific intestinal absorption of furosemide by Eudragit L100-55. J. Pharm. Pharmacol., 2001, 53(4), 433-440.
[] [PMID: 11341359]
Vlachou, M.; Papaïoannou, G. Preparation and characterization of the inclusion complex of furosemide with hydroxypropyl-β-cyclodextrin. J. Biomater. Appl., 2003, 17(3), 197-206.
[] [PMID: 12614084]
Deshmukh, A.; Nakhat, P.; Yeole, P. Formulation and in-vitro evaluation of self microemulsifying drug delivery system (SMEDDS) of Furosemide. Der Pharmacia Lettre, 2010, 2, 94-106.
Sambaraj, S.; Ammula, D.; Nagabandi, V. Furosemide loaded silica-lipid hybrid Microparticles: Formulation development, in vitro and ex vivo evaluation. Adv. Pharm. Bull., 2015, 5(3), 403-409.
[] [PMID: 26504763]
Hai, T.; Wana, X.; Yu, D.G.; Wang, K.; Yang, Y.; Liu, Z.P. Electrospun lipid-coated medicated nanocomposites for an improved drug sustained-release profile. Mater. Des., 2019, 162, 70-79.
Liu, X.; Yang, Y.; Yu, D.G.; Zhu, M.J.; Min, Z.; Williams, G.R. Tunable zero-order drug delivery systems created by modified triaxial electrospinning. Chem. Eng. J., 2019, 356, 886-894.
Yang, Y.; Li, W.; Yu, D.G.; Wang, G.; Williams, G.R.; Zhang, Z. Tunable drug release from nanofibers coated with blank cellulose acetate layers fabricated using tri-axial electrospinning. Carbohydr. Polym., 2019, 203, 228-237.
[] [PMID: 30318208]
Vlachou, M.; Geraniou, E.; Samidi, A. Modified release of furosemide from Eudragits® and poly(ethylene oxide)-based matrices and dry-coated tablets. Acta Pharm., 2019, 70(1), 49-61.
[] [PMID: 31677367]
Brodin, L.Å.; Jogestrand, T.; Larsen, F.F.; Tedner, B.; Walldius, G. Effects of furosemide and slow-release furosemide on thoracic fluid volumes. Clin. Cardiol., 1986, 9(11), 561-564.
[] [PMID: 3542323]
Efentakis, M.; Koutlis, A.; Vlachou, M. Development and evaluation of oral multiple-unit and single-unit hydrophilic controlled-release systems. AAPS PharmSciTech, 2000, 1(4)E34
[] [PMID: 14727899]
Jain, D.; Verma, S.; Shukla, S.B.; Jain, A.K.; Jain, P.; Yadav, P. Formulation and evaluation of gastroretentive tablets of Furosemide (Evaluation based on drug release kinetics and factorial designs). J. Chem. Pharm. Res., 2010, 2, 935-978.
Aceves, J.M.; Cruz, R.; Hernandez, E. Preparation and characterization of Furosemide-Eudragit controlled release systems. Int. J. Pharm., 2000, 195(1-2), 45-53.
[] [PMID: 10675682]
Ibrahim, M.A.; Abou El Ela, A.E.S.F. Optimized furosemide taste masked orally disintegrating tablets. Saudi Pharm. J., 2017, 25(7), 1055-1062.
[] [PMID: 29158715]
Vlachou, M.; Siamidi, A.; Konstantinidou, S.; Dotsikas, Y. Optimization of controlled release matrix formulation of melatonin via experimental design. J. Pharm. Drug Deliv. Res., 2016, 5, 1-5.
Vlachou, M.; Siamidi, A.; Efentakis, M. Investigation of a novel “tablets in capsule” theophylline formulation system for modified release. Pharm. Pharmacol. Int. J., 2017, 5, 1-7.
Vlachou, M.; Siamidi, A.; Diamantidi, E.; Iliopoulou, A.; Papanastasiou, I.; Ioannidou, V.; Kourbeli, V.; Foscolos, A.S.; Vocat, A.; Cole, S.T.; Karalis, V.; Kellici, T.; Mavromoustakos, T. In vitro controlled release from solid pharmaceutical formulations of two new adamantane aminoethers with antitubercular activity (I). Drug Res. (Stuttg.), 2017, 67(8), 447-450.
[] [PMID: 28561241]
Vlachou, M.; Siamidi, A.; Spaneas, D.; Lentzos, D.; Ladia, P.; Anastasiou, K.; Papanastasiou, I.; Foscolos, A.S.; Georgiadis, M.O.; Karalis, V.; Kellici, T.; Mavromoustakos, T. In vitro controlled release of two new tuberculocidal adamantane aminoethers from solid pharmaceutical formulations (II). Drug Res. (Stuttg.), 2017, 67(11), 653-660.
[] [PMID: 28724167]
Vlachou, M.; Papamichael, M.; Siamidi, A.; Fragouli, I.; Afroudakis, P.A.; Kompogennitaki, R.; Dotsikas, Y. Comparative In vitro controlled release studies on the chronobiotic hormone melatonin from cyclodextrins-containing matrices and Cyclodextrin: Melatonin complexes. Int. J. Mol. Sci., 2017, 18(8), 1641.
[] [PMID: 28788064]
Vlachou, M.; Tragou, K.; Siamidi, A.; Kikionis, S.; Chatzianagnostou, A.L.; Mitsopoulos, A.; Ioannou, E.; Roussis, V.; Tsotinis, A. Modified in vitro release of the chronobiotic hormone melatonin from matrix tablets based on the marine sulfated polysaccharide ulvan. J. Drug Deliv. Sci. Technol., 2018, 44, 41-48.
Vlachou, M.; Kikionis, S.; Siamidi, A.; Tragou, K.; Kapoti, S.; Ioannou, E.; Roussis, V.; Tsotinis, A. Fabrication and characterization of electrospun nanofibers for the modified release of the chronobiotic hormone melatonin. Curr. Drug Deliv., 2019, 16(1), 79-85.
[] [PMID: 30215335]
de Aguiar, X.P.F.; Bourguignon, B.; Khots, M.S.; Massart, D.L.; Phan-Than-Luu, R. D-optimal designs. Chemom. Intell. Lab. Syst., 1995, 30, 199-210.
Malenović, A.; Dotsikas, Y.; Mašković, M.; Jančić-Stojanović, B.; Ivanović, D.; Medenica, M. Desirability-based optimization and its sensitivity analysis for the perindopril and its impurities analysis in a microemulsion LC system. Microchem. J., 2011, 99, 454-460.
Terao, T.; Matsuda, K.; Shouji, H. Improvement in site-specifc intestinal absorption of furosemide by Eudragit L100-55. J. Pharm. Pharmacol., 2001, 53, 433-440.
[] [PMID: 11341359]
Han, M.; Yu, Q.; Liu, X.; Hu, F.; Yuan, H. Preparation and characterization of a novel aqueous dispersion for enteric coating of pantoprazole sodium pellets. Acta Pharm., 2018, 68(4), 441-455.
[] [PMID: 31259710]
Ibrahim, M.A.; Abou El Ela, A.E.S.F. Optimized furosemide taste masked orally disintegrating tablets. Saudi Pharm. J., 2017, 25(7), 1055-1062.
[] [PMID: 29158715]
Vo, A.Q.; Feng, X.; Morott, J.T.; Pimparade, M.B.; Tiwari, R.V.; Zhang, F.; Repka, M.A. A novel floating controlled release drug delivery system prepared by hot-melt extrusion. Eur. J. Pharm. Biopharm., 2016, 98, 108-121.
[] [PMID: 26643801]
Vlachou, M.; Siamidi, A.; Pareli, I.; Zampakola, A.; Konstantinidou, S. An Account of modified release of melatonin from compression-coated, uncoated and bilayer tablets. J. Pharm. Pharm. Sci., 2016, 1, 10-14.
Gavate, N.T.; Gondkar, S.B.; Saudagar, R.B. Multilayer tablet: A new trend in solid dosage forms. World J. Pharm. Pharm. Sci., 2013, 3, 271-284.
Momin, M.M.; Kane, S.; Abhang, P. Formulation and evaluation of bilayer tablet for bimodal release of venlafaxine hydrochloride. Front. Pharmacol., 2015, 6, 144.
[] [PMID: 26217229]
Marzan, A.L.; Tabassum, R.; Jahan, B.; Asif, M.H.; Reza, H.M.; Kazi, M.; Alshehri, S.M.; de Matas, M.; Shariare, M.H. Preparation and characterization of stable nanosuspension for dissolution rate enhancement of furosemide: A quality by design (QbD) approach. Curr. Drug Deliv., 2018, 15(5), 672-685.
[] [PMID: 29359667]
Goos, Y.P.; Jones, B.; Syafitri, U. I-optimal design of mixture experiments. J. Am. Stat. Assoc., 2016, 111, 899-911.
Khlibsuwan, R.; Pongjanyakul, T. Chitosan-clay matrix tablets for sustained-release drug delivery: Effect of chitosan molecular weight and lubricant. J. Drug Deliv. Sci. Technol., 2016, 35, 303-313.
Cismesia, A.P.; Nicholls, G.R.; Polfer, N.C. Amine vs. carboxylic acid protonation in ortho-, meta-, and para-aminobenzoic acid: An IRMPD spectroscopy study. J. Mol. Spectrosc., 2017, 332, 79-85.
[] [PMID: 28439142]
Rowe, R.C.; Sheskey, P.J.; Owen, S.C. Polymethacrylates. In Handbook of Pharmaceutical Excipients, 5th ed.; American Pharmaceutical Association and Pharmaceutical Press: London, 2006, 525-533.
Guzmán, M.L.; Manzo, R.H.; Olivera, M.E. Eudragit E100 as a drug carrier: The remarkable affinity of phosphate ester for dimethylamine. Mol. Pharm., 2012, 9(9), 2424-2433.
[] [PMID: 22808998]
Jin, M.; Yu, D.G.; Wang, X.; Geraldes, C.F.; Williams, G.R.; Bligh, S.W. Electrospun contrast-agent-loaded fibers for colon-targeted MRI. Adv. Healthc. Mater., 2016, 5(8), 977-985.
[] [PMID: 26899401]
Jin, M.; Yu, D.G.; Geraldes, C.F.G.C.; Williams, G.R.; Bligh, S.W. Theranostic fibers for simultaneous imaging and drug delivery. Mol. Pharm., 2016, 13(7), 2457-2465.
[] [PMID: 27280491]
Yu, D.G.; Li, H.P.; Yang, C.; Li, J.J.; Wang, Q.; Williams, G.R. Double-pulsatile release core-shell fibers fabricated using modified tri-axial electrospinning. J. Control. Release, 2017, 259, e24-e25.
Mourão, S.C.; da Silva, C.; Bresolin, T.M.B.; Serra, C.H.R.; Porta, V. Dissolution parameters for sodium diclofenac-containing hypromellose matrix tablet. Int. J. Pharm., 2010, 386(1-2), 201-207.
[] [PMID: 19941944]
Wang, Q.; Yu, D.G.; Zhang, L.L.; Liu, X.K.; Deng, Y.C.; Zhao, M. Electrospun hypromellose-based hydrophilic composites for rapid dissolution of poorly water-soluble drug. Carbohydr. Polym., 2017, 174, 617-625.
[] [PMID: 28821112]
Yu, D.G.; Li, J.J.; Williams, G.R.; Zhao, M. Electrospun amorphous solid dispersions of poorly water-soluble drugs: A review. J. Control. Release, 2018, 292, 91-110.
[] [PMID: 30118788]

Rights & Permissions Print Export Cite as
© 2024 Bentham Science Publishers | Privacy Policy