Formulation and evaluation of delayed-onset extended-release tablets of metoprolol tartrate using hydrophilic-swellable polymers

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Formulation and evaluation of delayed-onset extended-release tablets of metoprolol tartrate using hydrophilic-swellable polymers

In view of the circadian rhythm of cardiovascular diseases, a delayed-onset extended-release (DOER) formulation of metoprolol tartrate (MT) was prepared. This was achieved through dissolution-guided optimization of the proportion of Methocel K4M and Methocel K15M. Core erosion ratio was greater than 50 %, thereby showing steady release of the drug after the lag time until complete dissolution. Optimized formulation produced a lag phase of 6 h followed by complete release of 98.7 ± 2.1 % in 24 h. Water uptake study revealed that Methocel K15M has lower water uptake (30 ± 1 %) than Methocel K4M (40 ± 2 %) after 24 h. Axial swelling of polymers was higher than swelling in the radial direction. Drug-polymer interaction study precludes any interaction between drug and polymer. Such a drug delivery system may provide a viable alternative for effective management of hypertension and other related disorders. This work also proposes an approach to attain DOER for a hydrophilic drug by using a hydrophilic swellable polymer in press coat.

B. Lemmer and G. Labrecque, Chronopharmacology and chronotherapeutics: definitions and concepts, Chronobiol. Int. 4 (1987) 319-329; DOI: 10.3109/07420528709083522.

S. N. Willich, D. Levy, M. B. Rocco, G. H. Tofler, P. H. Stone and J. E. Muller, Circadian variation in the incidence of sudden cardiac death in the Framingham Heart Study Population, Am. J. Cardiol. 60 (1987) 801-806; DOI: 10.1016/0002-9149(87)91027-7.

M. W. Millar-Crag, C. N. Bishop and E. B. Raftery, Circadian variation of blood-pressure, Lancet 311 (1978) 795-797; DOI: 10.1016/S0140-6736(78)92998-7.

K. Kario, T. Matsuo, H. Kobayashi, M. Imiya, M. Matsuo and K. Shimada, Nocturnal fall of blood pressure and silent cerebrovascular damage in elderly hypertensive patients, Hypertension 27 (1996) 130-135.

S. P. Boldhane and B. S. Kuchekar, Development and optimization of metoprolol succinate gastroretentive drug delivery system, Acta Pharm. 60 (2010) 415-425; DOI: 10.2478/v10007-010-0031-x.

H. Zou, X. Jiang, L. Kong and S. Gao, Design and evaluation of a dry coated drug delivery system with floating-pulsatile release, J. Pharm. Sci. 97 (2008) 263-273; DOI: 10.1002/jps.21083.

D. S. Hanes and M. R. Weir, The beta blockers: are they as protective in hypertension as in other cardiovascular conditions? J. Clin. Hypertens. 3 (2001) 236-243; DOI: 10.1111/j.1524-6175.2001.00444.x.

Indian Pharmacopoeia, 6 th ed., Government of India, Ministry of Health and Family Welfare, Delhi 2010, pp. 1681-1683.

J. T. Fell and J. M. Newton, Determination of tablet strength by the diametral-compression test, J. Pharm. Sci. 59 (1970) 688-691; DOI: 10.1002/jps.2600590523.

J. Nunthanid, M. Luangtana-anan, P. Sriamornsak, S. Limmatvapirat, K. Huanbutta and S. Puttipipatkhachorn, Use of spray-dried chitosan acetate and ethylcellulose as compression coats for colonic drug delivery: effect of swelling on triggering in vitro drug release, Eur. J. Pharm. Biopharm. 71 (2009) 356-361; DOI: 10.1016/j.ejpb.2008.08.002.

T. Sawada, K. Sako, M. Fukui, S. Yokohama and M. Hayashi, A new index, the core erosion ratio, of compression-coated timed-release tablets predicts the bioavailability of acetaminophen, Int. J. Pharm. 265 (2003) 55-63; DOI: 10.1016/S0378-5173(03)00405-8.

United States Pharmacopeia XXXII, National Formulary XXVII, USP Convention, Rockville (MD) 2009, pp. 263-275.

T. Higuchi, Mechanism of sustained-action medication: theoretical analysis of rate of release of solid drugs dispersed in solid matrices, J. Pharm. Sci. 52 (1963) 1145-1149; DOI: 10.1002/jps.2600521210.

R. W. Korsmeyer, R. Gurny, E. Doelker, P. Buri and N. A. Peppas, Mechanisms of solute release from porous hydrophilic polymers, Int. J. Pharm. 15 (1983) 25-35; DOI: 10.1016/0378-5173(83)90064-9.

L. W. Cheong, P. W. S. Heng and L. F. Wong, Relationship between polymer viscosity and drug release from a matrix system, Pharm. Res. 9 (1992) 1510-1514; DOI: 10.1023/A:1015883501871.

C. Dahlberg, A. Fureby, M. Schuleit, S. V. Dvinskikh and I. Furo, Polymer mobilization and drug release during tablet swelling, A 1H NMR and NMR microimaging study, J. Control. Release 122 (2007) 199-205; DOI: 10.1016/j.jconrel.2007.07.007.

J. Siepmann and N. A. Peppas, Modeling of drug release from delivery system based on hydroxypropyl methylcellulose (HPMC), Adv. Drug Deliv. Rev. 48 (2001) 139-157; DOI: 10.1016/S0169-409X(01)00112-0.

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