Study the effect of formulation variables in the development of timed-release press-coated tablets by Taguchi design
ABSTRACT
In this investigation, the effect of formulation variables on the release properties of timed- release press-coated tablets was studied using the Taguchi method of experimental design. Formulations were prepared based on Taguchi orthogonal array design with different types of hydrophilic polymers (X1), varying hydrophilic polymer/ethyl cellulose ratio (X2), and addition of magnesium stearate (X3) as independent variables. The design was quantitatively evalu-ated by best fit mathematical model. The results from the statistical analysis revealed that factor X1, X3 and interaction factors between X1X2 and X1X3 were found to be significant on the re-sponse lag time (Y1), where as only factor X1 was found to be significant on the response percent drug release at 8 hrs (Y2). A numerical optimization technique by desirability function was used to optimize the response variables, each having a different target. Based on the re-sults of optimization study, HPC was identified as the most suitable hydrophilic polymer and incorporation of hydrophobic agent magnesium stearate, could significantly improve the lag time of the timed-release press-coated tablet.
In this investigation, the effect of formulation variables on the release properties of timed- release press-coated tablets was studied using the Taguchi method of experimental design. Formulations were prepared based on Taguchi orthogonal array design with different types of hydrophilic polymers (X1), varying hydrophilic polymer/ethyl cellulose ratio (X2), and addition of magnesium stearate (X3) as independent variables. The design was quantitatively evalu-ated by best fit mathematical model. The results from the statistical analysis revealed that factor X1, X3 and interaction factors between X1X2 and X1X3 were found to be significant on the re-sponse lag time (Y1), where as only factor X1 was found to be significant on the response percent drug release at 8 hrs (Y2). A numerical optimization technique by desirability function was used to optimize the response variables, each having a different target. Based on the re-sults of optimization study, HPC was identified as the most suitable hydrophilic polymer and incorporation of hydrophobic agent magnesium stearate, could significantly improve the lag time of the timed-release press-coated tablet.
KEYWORDS
Press-Coated Tablet; Taguchi Design; Hydrophilic Polymers; Timed-Release; Hydrophobic Agents
Press-Coated Tablet; Taguchi Design; Hydrophilic Polymers; Timed-Release; Hydrophobic Agents
Cite this paper
Narendra, C. and Srinath, M. (2010) Study the effect of formulation variables in the development of timed-release press-coated tablets by Taguchi design. Natural Science, 2, 379-387. doi: 10.4236/ns.2010.24046.
Narendra, C. and Srinath, M. (2010) Study the effect of formulation variables in the development of timed-release press-coated tablets by Taguchi design. Natural Science, 2, 379-387. doi: 10.4236/ns.2010.24046.
References
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[6] Crison, J.R., Siersma, P.R., Taylor, M.D. and Amidon, G.L. (1995) Programmable oral release technology, Port Systems & Mac226: A novel dosage form for time and site specific oral drug delivery. Proceedings of Interna-tional Symposium on Control Release of Bioactive Mate-rials, 22, 278-279. [7] Conte, U., Maggi, L., Torre, P., Giunchedi, P. and La-Manna, A. (1993) Press-coated tablets for time pro-grammed release of drugs. Biomaterials, 14(13), 1017- 1023. [8] Conte, U. and Maggi, L. (1996) Modulation of the dis-solution profiles from Geomatrix® multi-layer matrix tablets containing drugs of different solubility. Biomate-rials, 17(9), 889-896. [9] Lemmer, B. (2007) Chronobiology, drug-delivery, and chronotherapeutics. Advanced Drug Delivery Reviews, 59(9-10), 825-827. [10] Wu, B., Shun, N., Wei, X. and Wu, W. (2007) Charac-terization of 5-fluorouracil release from hydroxypropyl-methylcellulose compression-coated tablets. Pharmaceu-tical Development and Technology, 12(2), 203-210. [11] Fukui, E., Uemura, K. and Kobayashi, M. (2000) Studies on applicability of press-coated tablets using hy-droxypropylcellulose (HPC) in the outer shell for timed- release preparations. Journal of Controlled Release, 68(2), 215-223. [12] Matsuo, M., Arimori, K., Nakamura, C. and Nakano, M. (1996) Delayed-release tablets using hydroxyethylcellu-lose as a gel-forming matrix. International Journal of Pharmaceutics, 138(2), 225-235. [13] Sawada, T., Kondo, H., Nakashima, H., Sako, K. and Hayashi, M. (2004) Time-release compression-coated core tablet containing nifedipine for chronopharmaco-therapy. International Journal of Pharmaceutics, 280(1-2), 103-111. [14] Ugurlu, T., Turkoglu, M., Gurer, U.S. and Akarsu, B.G. (2007) Colonic delivery of compression coated nisin tablets using pectin/HPMC polymer mixture. European Journal of Pharmaceutics and Biopharmaceutics, 67(1), 202-210. [15] Lin, S.Y., Li, M.J. and Lin, K.H. (2004) Hydrophilic excipients modulate the time lag of time-controlled dis-integrating press-coated tablets. AAPS PharmSciTech, 5(4), Article 54. [16] Fukui, E., Miyamura, N., Yoneyama, T. and Kobayashi, M. (2001) Drug release from and mechanical properties of press-coated tablets with hydroxypropylmethylcellu-lose acetate succinate and plasticizers in the outer shell. International Journal of Pharmaceutics, 217(1-2), 33-43. [17] Fukui, E., Miyamura, N. and Kobayashi, M. (2001) Ef-fect of magnesium stearate or calcium stearate as addi-tives on dissolution profiles of diltiazem hydrochloride from press-coated tablets with hydroxypropylmethylcel-lulose acetate succinate in the outer shell. International Journal of Pharmaceutics, 216(1-2), 137-146. [18] Narendra, C., Srinath M.S. and Rao, B.P. (2005) Devel-opment of three layered buccal compact containing metoprolol tartrate by statistical optimization technique. International Journal of Pharmaceutics, 304(1-2), 102- 114. [19] Lewis, G.A., Mathieu, D. and Phan-Tan-Luu, R. (1999) Pharmaceutical experimental design. Marcel Dekker, New York. [20] Li, S., Lin, S., Daggy, B.P., Mirchandani, H.L. and Chein, Y.W. (2003) Effect of HPMC and carbopol on the release and floating properties of gastric floating drug delivery system using factorial design. International Journal of Pharmaceutics, 253(1-2), 13-22. [21] Nouranian, S., Garambi, H. and Mohammadi, N. (2007) Taguchi-based optimization of adhesion of polyurethane to plasticized poly (vinyl chloride) in synthetic leather. Journal of Adhesion Science and Technology, 21(8), 705- 724. [22] Conti, S., Maggia, L., Segalea, L., Machiste, E.O., Conte, U., Grenier, P. and Vergnault, G. (2007) Matrices con-taining NaCMC and HPMC 1. Dissolution performance characterization. International Journal of Pharmaceutics, 333(1-2), 136-142. [23] Matsuo, M., Nakamura, C., Arimori, K. and Nakano, M. (1995) Evaluation of hydroxyethylcellulose as a hydro-philic swellable material for delayed release tablets. Chemical & Pharmaceutical Bulletin, 43(2), 311-314. [24] Mahato, R.I. (2005) Biomaterials for delivery and tar-geting of proteins and nucleic acids. CRC Press, Florida. [25] Enayatifard, R., Saeedi, M., Akbari, J. and Tabatabaee, Y.H. (2009) Effect of hydroxypropylmethylcellulose and ethylcellulose content on release profile and kinetics of dilti-azem hcl from matrices. Tropical Journal of Pharmaceutical Research, 8(5), 425-432. [26] Roy, D.S. and Rohera, B.D. (2002) Comparative evalua-tion of rate of hydration and matrix erosion of HEC and HPC and study of drug release from their matrices. European Journal of Pharmaceutical Sciences, 16(3), 193-199. [27] Hilton, A.K. and Deasy, P.B. (1992) In vitro and in vivo evaluation of an oral sustained-release floating dosage form of amoxycillin trihydrate. International Journal of Pharmaceutics, 86(1), 79-88. [28] Durig, T. and Fassihi, R. (1997) Mechanistic evaluation of binary effects of magnesium stearate and talc as dis-solution retardants at 85% drug loading in an experimen-tal extended-release formulation. Journal of Pharmaceu-tical Sciences, 86(10), 1092-1098. [29] Minarro, M., Garcia-Montoya, E. and Sune-Negre, J.M. (2001) Study of formulation parameters by factorial de-sign in metoprolol tartrate matrix systems. Drug Devel-opment and Industrial Pharmacy, 27(9), 965-973. [30] Narendra, C., Srinath, M.S. and Moin, A. (2008) Study the effect of formulation variables on in vitro floating time and release properties of floating drug delivery sys-tem by statistical optimization technique. Chemical In-dustry & Chemical Engineering Quarterly, 14, 17-26. [31] Sanchez-Lafuente, C., Furlanetto, S., Fernandez-Arevalo, M., Alvarez-Fuentes, J., Rabasco, A.M., Faucci, T., Pin-zauti, S. and Mura, P. (2002) Didanosine extended- re-lease matrix tablets: Optimization of formulation vari-ables using statistical experimental design. International Journal of Pharmaceutics, 237(1-2), 107-118. [32] Kuo, C.F.J. and Wu, Y.-S. (2006) Optimization of the film coating process for polymer blends by the grey- based Taguchi method. International Journal of Ad-vanced Manufacturing Technology, 27(5-6), 525-530.
[1] Ueda, S., Hata, T., Asakura, S., Yamaguchi, H., Kotani, M. and Ueda, Y. (1994) Development of a novel drug release system, time-controlled explosion system (TES). I. Con-cept and design. Journal of Drug Targeting, 2(1), 35-44. [2] Krögel, I. and Bodmeier, R. (1998) Pulsatile drug release from an insoluble capsule body controlled by an erodible plug. Pharmaceutical Research, 15(3), 474-481. [3] Pozzi, F., Furlani, P., Gazzaniga, A., Davis, S.S. and Wilding, I.R. (1994) The TIME CLOCK* system: A new oral dosage form for fast and complete release of drug after a predetermined lag time. Journal of Controlled Release, 31(1), 99-108. [4] Gazzaniga A., Sangalli, M. and Giordano, F. (1994) Oral chronotropic drug delivery systems: Achievement of time and/or site specificity. European Journal of Pharmaceu-tics and Biopharmaceutics, 40, 246-250. [5] McNeil, M.E., Rashid, A. and Stevens, H.N.E. (1994) Dispensing device. U.S. Patent 5,342,624. [6] Crison, J.R., Siersma, P.R., Taylor, M.D. and Amidon, G.L. (1995) Programmable oral release technology, Port Systems & Mac226: A novel dosage form for time and site specific oral drug delivery. Proceedings of Interna-tional Symposium on Control Release of Bioactive Mate-rials, 22, 278-279. [7] Conte, U., Maggi, L., Torre, P., Giunchedi, P. and La-Manna, A. (1993) Press-coated tablets for time pro-grammed release of drugs. Biomaterials, 14(13), 1017- 1023. [8] Conte, U. and Maggi, L. (1996) Modulation of the dis-solution profiles from Geomatrix® multi-layer matrix tablets containing drugs of different solubility. Biomate-rials, 17(9), 889-896. [9] Lemmer, B. (2007) Chronobiology, drug-delivery, and chronotherapeutics. Advanced Drug Delivery Reviews, 59(9-10), 825-827. [10] Wu, B., Shun, N., Wei, X. and Wu, W. (2007) Charac-terization of 5-fluorouracil release from hydroxypropyl-methylcellulose compression-coated tablets. Pharmaceu-tical Development and Technology, 12(2), 203-210. [11] Fukui, E., Uemura, K. and Kobayashi, M. (2000) Studies on applicability of press-coated tablets using hy-droxypropylcellulose (HPC) in the outer shell for timed- release preparations. Journal of Controlled Release, 68(2), 215-223. [12] Matsuo, M., Arimori, K., Nakamura, C. and Nakano, M. (1996) Delayed-release tablets using hydroxyethylcellu-lose as a gel-forming matrix. International Journal of Pharmaceutics, 138(2), 225-235. [13] Sawada, T., Kondo, H., Nakashima, H., Sako, K. and Hayashi, M. (2004) Time-release compression-coated core tablet containing nifedipine for chronopharmaco-therapy. International Journal of Pharmaceutics, 280(1-2), 103-111. [14] Ugurlu, T., Turkoglu, M., Gurer, U.S. and Akarsu, B.G. (2007) Colonic delivery of compression coated nisin tablets using pectin/HPMC polymer mixture. European Journal of Pharmaceutics and Biopharmaceutics, 67(1), 202-210. [15] Lin, S.Y., Li, M.J. and Lin, K.H. (2004) Hydrophilic excipients modulate the time lag of time-controlled dis-integrating press-coated tablets. AAPS PharmSciTech, 5(4), Article 54. [16] Fukui, E., Miyamura, N., Yoneyama, T. and Kobayashi, M. (2001) Drug release from and mechanical properties of press-coated tablets with hydroxypropylmethylcellu-lose acetate succinate and plasticizers in the outer shell. International Journal of Pharmaceutics, 217(1-2), 33-43. [17] Fukui, E., Miyamura, N. and Kobayashi, M. (2001) Ef-fect of magnesium stearate or calcium stearate as addi-tives on dissolution profiles of diltiazem hydrochloride from press-coated tablets with hydroxypropylmethylcel-lulose acetate succinate in the outer shell. International Journal of Pharmaceutics, 216(1-2), 137-146. [18] Narendra, C., Srinath M.S. and Rao, B.P. (2005) Devel-opment of three layered buccal compact containing metoprolol tartrate by statistical optimization technique. International Journal of Pharmaceutics, 304(1-2), 102- 114. [19] Lewis, G.A., Mathieu, D. and Phan-Tan-Luu, R. (1999) Pharmaceutical experimental design. Marcel Dekker, New York. [20] Li, S., Lin, S., Daggy, B.P., Mirchandani, H.L. and Chein, Y.W. (2003) Effect of HPMC and carbopol on the release and floating properties of gastric floating drug delivery system using factorial design. International Journal of Pharmaceutics, 253(1-2), 13-22. [21] Nouranian, S., Garambi, H. and Mohammadi, N. (2007) Taguchi-based optimization of adhesion of polyurethane to plasticized poly (vinyl chloride) in synthetic leather. Journal of Adhesion Science and Technology, 21(8), 705- 724. [22] Conti, S., Maggia, L., Segalea, L., Machiste, E.O., Conte, U., Grenier, P. and Vergnault, G. (2007) Matrices con-taining NaCMC and HPMC 1. Dissolution performance characterization. International Journal of Pharmaceutics, 333(1-2), 136-142. [23] Matsuo, M., Nakamura, C., Arimori, K. and Nakano, M. (1995) Evaluation of hydroxyethylcellulose as a hydro-philic swellable material for delayed release tablets. Chemical & Pharmaceutical Bulletin, 43(2), 311-314. [24] Mahato, R.I. (2005) Biomaterials for delivery and tar-geting of proteins and nucleic acids. CRC Press, Florida. [25] Enayatifard, R., Saeedi, M., Akbari, J. and Tabatabaee, Y.H. (2009) Effect of hydroxypropylmethylcellulose and ethylcellulose content on release profile and kinetics of dilti-azem hcl from matrices. Tropical Journal of Pharmaceutical Research, 8(5), 425-432. [26] Roy, D.S. and Rohera, B.D. (2002) Comparative evalua-tion of rate of hydration and matrix erosion of HEC and HPC and study of drug release from their matrices. European Journal of Pharmaceutical Sciences, 16(3), 193-199. [27] Hilton, A.K. and Deasy, P.B. (1992) In vitro and in vivo evaluation of an oral sustained-release floating dosage form of amoxycillin trihydrate. International Journal of Pharmaceutics, 86(1), 79-88. [28] Durig, T. and Fassihi, R. (1997) Mechanistic evaluation of binary effects of magnesium stearate and talc as dis-solution retardants at 85% drug loading in an experimen-tal extended-release formulation. Journal of Pharmaceu-tical Sciences, 86(10), 1092-1098. [29] Minarro, M., Garcia-Montoya, E. and Sune-Negre, J.M. (2001) Study of formulation parameters by factorial de-sign in metoprolol tartrate matrix systems. Drug Devel-opment and Industrial Pharmacy, 27(9), 965-973. [30] Narendra, C., Srinath, M.S. and Moin, A. (2008) Study the effect of formulation variables on in vitro floating time and release properties of floating drug delivery sys-tem by statistical optimization technique. Chemical In-dustry & Chemical Engineering Quarterly, 14, 17-26. [31] Sanchez-Lafuente, C., Furlanetto, S., Fernandez-Arevalo, M., Alvarez-Fuentes, J., Rabasco, A.M., Faucci, T., Pin-zauti, S. and Mura, P. (2002) Didanosine extended- re-lease matrix tablets: Optimization of formulation vari-ables using statistical experimental design. International Journal of Pharmaceutics, 237(1-2), 107-118. [32] Kuo, C.F.J. and Wu, Y.-S. (2006) Optimization of the film coating process for polymer blends by the grey- based Taguchi method. International Journal of Ad-vanced Manufacturing Technology, 27(5-6), 525-530.