Development of Optimal Extended-Release Formulations for Poorly Water-Soluble Drug (Mefenamic Acid) Using Quality by Design Principles
Article Sidebar
Main Article Content
Abstract
The aim of this project was to develop optimal extended-release tablets of mefenamic acid using the principles of Quality by Design (QbD). Mefenamic acid is a poorly water-soluble drug, classified as a BCS Class II drug (low solubility, high permeability). The formulations were designed using the Design of Experiment (DoE) feature of JMP software. Lactose, in the range of 15–25%, was used as a filler, while HPMC K100M, in the range of 10–15%, was used as a modified-release agent to design 12 different formulations. Various physical parameters of the tablets, namely thickness, diameter, hardness, friability, and in vitro release, were evaluated. The physical parameters of the compressed tablets were found to be satisfactory for all formulations. In vitro drug release studies were performed in 900 mL of phosphate buffer medium at pH 7.1 containing 2% cetyltrimethyl ammonium bromide (CTAB) using a dissolution apparatus (paddle method). The in vitro release profiles indicated that all formulations of mefenamic acid functioned effectively as extended-release tablets. The drug release percentage of all formulations met the Quality Target Product Profile (QTPP) goal of achieving 50–85% drug release within six hours.
Article Details
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
References
Allen, C. T., Sephen, R. B., Roy, J. H. and Thomas, E. P., 2014. Discovering and developing molecules with optimal drug-like properties. USA: Department of Industrial and Physical Pharmacy.
Anand, O., Yu, L.X., Conner, D.P. and Davit, B.M. 2011, "Dissolution Testing for Generic Drugs: An FDA Perspective", The AAPS Journal, vol. 13, no. 3, pp. 328-335.
Aulton, M.E. and Taylor, K. 2013, Aulton's pharmaceutics: the design and manufacture of medicines, 4th edn, Churchill Livingstone/Elsevier, Edinburgh.
Barakat, N.S., Elbagory, I.M. and Almurshedi, A.S. 2009, "Controlled-release carbamazepine matrix granules and tablets comprising lipophilic and hydrophilic components", Drug Delivery, vol. 16, no. 1, pp. 57-65.
Basalious, E.B., El-Sebaie, W. and El-Gazayerly, O. 2011, "Application of Pharmaceutical QbD for Enhancement of the Solubility and Dissolution of a Class II BCS Drug using Polymeric Surfactants and Crystallization Inhibitors: Development of Controlled-Release Tablets", AAPS PharmSciTech, vol. 12, no. 3, pp. 799-810.
Baviskar, D., Sharma, R. and Jain, D. 2013, "Modulation of drug release by utilizing pH-independent matrix system comprising water soluble drug verapamil hydrochloride", Pakistan Journal of Pharmaceutical Sciences, vol. 26, no. 1, pp. 137-144.
Benet, L.Z. 2013, "The role of BCS (biopharmaceutics classification system) and BDDCS (biopharmaceutics drug disposition classification system) in drug development", Journal of Pharmaceutical Sciences, vol. 102, no. 1, pp. 34-42.
Bose, A., Wong, T.W. and Singh, N. 2013, "Formulation development and optimization of sustained release matrix tablet of Itopride HCl by response surface methodology and its evaluation of release kinetics", Saudi Pharmaceutical Journal, vol. 21, no. 2, pp. 201-213.
Brittain, H.G. 2006, "A Review of: 'Handbook of Dissolution Testing, 3rd edition'", Pharmaceutical Development and Technology, vol. 11, no. 3, pp. 401-402.
Chan, C.C. 2004, Analytical Method Validation and Instrument Performance Verification, 1st edn, Interscience, US.
Felton, L.A., Remington, J.P. and Philadelphia College of Pharmacy 2013, Remington Essentials of Pharmaceutics, Pharmaceutical Press, London.
Huang, J., Wigent, R.J., Bentzley, C.M. and Schwartz, J.B. 2006, "Nifedipine solid dispersion in microparticles of ammonio methacrylate copolymer and ethylcellulose binary blend for controlled drug delivery", International Journal of Pharmaceutics, vol. 319, no. 1, pp. 44-54.
Huang, Y., Tsai, Y., Yang, W., Chang, J. and Pao-Chu, W.U. 2004, "Optimization of sustained-release propranolol dosage form using factorial design and response surface methodology", Biological and Pharmaceutical Bulletin, vol. 27, no. 10, 1626-1629.
Hühn, E. and Langguth, P. 2013, "In vitro-in vivo correlations", Pharmazeutische Industrie, vol. 75, no. 1, pp. 143-152.
Husen, P.M., Ashok Kumar, P., Kulkarni, S.V. and Someshwara Rao, B. 2012, "Formulation and in vitro evaluation of controlled release matrix tablets of metoclopramide hydrochloride: Influence of fillers on hydrophilic natural gums", International Journal of Pharmacy and Pharmaceutical Sciences, vol. 4, no. 4, pp. 181-187.
Jorgensen, E.D. and Bhagwat, D. 1998, "Development of dissolution tests for oral extended-release products", Pharmaceutical Science and Technology Today, vol. 1, no. 3, pp. 128-135.
Kaul, G., Huang, J., Chatlapalli, R., Ghosh, K. and Nagi, A. 2011, "Quality-by-Design Case Study: Investigation of the Role of Poloxamer in Immediate-Release Tablets by Experimental Design and Multivariate Data Analysis", AAPS PharmSciTech, vol. 12, no. 4, pp. 1064-1076.
Kerns, E.H. and Di, L. 2008, Drug-Like Properties: Concepts, Structure Design and Methods, Academic Press, USA.
Kiortsis, S., Kachrimanis, K., Broussali, T. and Malamataris, S. 2005, "Drug release from tableted wet granulations comprising cellulosic (HPMC or HPC) and hydrophobic component", European Journal of Pharmaceutics and Biopharmaceutics, vol. 59, no. 1, pp. 73-83.
Leuner, C. and Dressman, J. 2000, "Improving drug solubility for oral delivery using solid dispersions", European Journal of Pharmaceutics and Biopharmaceutics, vol. 50, no. 1, pp. 47-60.
Peter, T., Samuel, R. P. and Colin, D. M. 2014, Hydrophilic Matrix Tablets for Oral Controlled Release, School of Pharmacy, Nottingham.
Rekhi, G.S., Nellore, R.V., Hussain, A.S., Tillman, L.G., Malinowski, H.J. and Augsburger, L.L. 1999, "Identification of critical formulation and processing variables for metoprolol tartrate extended-release (ER) matrix tablets", Journal of Controlled Release, vol. 59, no. 3, pp. 327-342.
Remington, J.P., Hendrickson, R. and University of the Sciences in Philadelphia 2006, Remington: The Science and Practice of Pharmacy, 21st edn, Lippincott Williams and Wilkins, Philadelphia.
Reza, M.S., Quadir, M.A. and Haider, S.S. 2003, "Comparative evaluation of plastic, hydrophobic and hydrophilic polymers as matrices for
controlled-release drug delivery", Journal of Pharmacy and Pharmaceutical Sciences, vol. 6, no. 2, pp. 282-291.
Sangshetti, J.N., Deshpande, M., Arote, R., Zaheer, Z. and Shinde, D.B. 2014, "Quality by design approach: Regulatory need", Arabian Journal of Chemistry, vol. 10, no. 2, pp. S3412-S3425.
Siddiqui, A. and Nazzal, S. 2007, "Measurement of surface color as an expedient QC method for the detection of deviations in tablet hardness", International Journal of Pharmaceutics, vol. 341, no. 1, pp. 173-180.
Singh, G., Pai, R.S. and Kusum Devi, V. 2012, "Response surface methodology and process optimization of sustained release pellets using Taguchi orthogonal array design and central composite design", Journal of Advanced Pharmaceutical Technology and Research, vol. 3, no. 1, pp. 30-40.
Skoug, J.W., Mikelsons, M.V., Vigneron, C.N. and Stemm, N.L. 1993, "Qualitative evaluation of the mechanism of release of matrix sustained release dosage forms by measurement of polymer release", Journal of Controlled Release, vol. 27, no. 3, pp. 227-245.
Wan, S., Sun, Y., Qi, X. and Tan, F. 2012, "Improved Bioavailability of Poorly Water-Soluble Drug Curcumin in Cellulose Acetate Solid Dispersion", AAPS PharmSciTech, vol. 13, no. 1, pp. 159-166.
Zheng, J. 2009, Formulation and Analytical Development for Low-Dose Oral Drug Products, 1st edn, Wiley, USA.