Dissolution stability over the entire shelf life duration is of critical importance to ensure the quality of solid dosage forms. Changes in the drug release profile during storage may affect the bioavailability of drug products. This study investigated the stability of a commercial tablet (Lescolr XL) when stored under accelerated conditions (40 oC/75% r.h.). Terahertz pulsed imaging (TPI) was used to investigate the structure of the tablet coating before and after the accelerated aging process. The results indicate that the coating was reduced in thickness and exhibited a higher density after being stored under accelerated conditions for four weeks. In situ magnetic resonance imaging (MRI) of the water penetration processes during tablet dissolution in a USP-IV dissolution cell equipped with an in-line UV-vis analyzer was carried out to study local differences in water uptake into the tablet matrix between the stressed and unstressed state. The drug release profiles of the Lescolr XL tablet before and after the accelerated storage stability testing were compared using a “difference” factor ∫1 and a “similarity” factor ∫2. The results reveal that even though the physical properties of the coating layers changed significantly during the stress testing, the coating protected the tablet matrix and the densification of the coating polymer had no adverse effect on the drug release performance.
References
[1]
Melveger, A.J.; Huynh-Ba, K. Critical Regulatory Requirements for a Stability Program. In Handbook of Stability Testing in Pharmaceutical Development; Springer: New York, NY, USA, 2009; pp. 9–19.
[2]
Risha, P.G.; Vervaet, C.; Vergote, G.; van Bortel, L.; Remon, J.P. Drug formulations intended for the global market should be tested for stability under tropical climatic conditions. Eur. J. Clin. Pharmacol. 2003, 59, 135–141.
[3]
Papandreou, G.; Zorpas, K.; Archontaki, H. Development and validation of a liquid chromatographic method for the simultaneous determination of aniracetam and its related substances in the bulk drug and a tablet formulation. Chem. Phys. Lett. 2011, 56, 615–622.
[4]
Süvegh, K.; Zelkó, R. Physical aging of poly(vinylpyrrolidone) under different humidity conditions. Macromolecules 2002, 35, 795–800, doi:10.1021/ma011148l.
[5]
Goskonda, V.R.; Reddy, I.K.; Durrani, M.J.; Wilber, W.; Khan, M.A. Solid-state stability assessment of controlled release tablets containing Carbopol？ 971P. J. Control. Release 1998, 54, 87–93, doi:10.1016/S0168-3659(97)00209-5.
[6]
Waterman, K.C.; MacDonald, B.C. Package selection for moisture protection for solid, oral drug products. J. Pharm. Sci. 2010, 99, 4437–4452, doi:10.1002/jps.22161.
[7]
Murthy, K.S.; Ghebre-Sellassie, I. Current perspectives on the dissolution stability of solid oral dosage forms. J. Pharm. Sci. 1993, 82, 113–126, doi:10.1002/jps.2600820202.
[8]
Krishnaiah, Y.S.R.; Karthikeyan, R.S.; Gouri Sankar, V.; Satyanarayana, V. Three-layer guar gum matrix tablet formulations for oral controlled delivery of highly soluble trimetazidine dihydrochloride. J. Control. Release 2002, 81, 45–56, doi:10.1016/S0168-3659(02)00031-7.
[9]
Nafee, N.A.; Ismail, F.A.; Boraie, N.A.; Mortada, L.M. Mucoadhesive buccal patches of miconazole nitrate: In vitro/in vivo performance and effect of ageing. Int. J. Pharm. 2003, 264, 1–14, doi:10.1016/S0378-5173(03)00371-5.
[10]
Rohrs, B.; Thamann, T.; Gao, P.; Stelzer, D.; Bergren, M.; Chao, R. Tablet dissolution affected by a moisture mediated solid-state interaction between drug and disintegrant. Pharm. Res. 1999, 16, 1850–1856, doi:10.1023/A:1018951309506.
[11]
Wang, J.T.; Shiu, G.K.; Ong-Chen, T.; Viswanathan, C.T.; Skelly, J.P. Effects of humidity and temperature on in vitro dissolution of carbamazepine tablets. J. Pharm. Sci. 1993, 82, 1002–1005, doi:10.1002/jps.2600821006.
[12]
Hirasawa, N.; Ishise, S.; Miyata, H.; Danjo, K. An attempt to stabilize nilvadipine solid dispersion by the use of ternary systems. Drug Dev. Ind. Pharm. 2003, 29, 997–1004, doi:10.1081/DDC-120025456.
Zeitler, J.A.; Gladden, L.F. In vitro tomography and non-destructive imaging at depth of pharmaceutical solid dosage forms. Eur. J. Pharm. Biopharm. 2009, 71, 2–22, doi:10.1016/j.ejpb.2008.08.012.
[15]
Ho, L.; Mueller, R.; Gordon, K.C.; Kleinebudde, P.; Pepper, M.; Rades, T.; Shen, Y.; Taday, P.F.; Zeitler, J.A. Applications of terahertz pulsed imaging to sustained-release tablet film coating quality assessment and dissolution performance. J. Control. Release 2008, 127, 79–87, doi:10.1016/j.jconrel.2008.01.002.
[16]
Shen, Y.; Taday, P.F. Development and application of terahertz pulsed imaging for nondestructive inspection of pharmaceutical tablet. IEEE J. Sel Top. Quantum Electron. 2008, 14, 407–415, doi:10.1109/JSTQE.2007.911309.
[17]
Zhang, Q.; Gladden, L.F.; Avalle, P.; Mantle, M. In vitro quantitative 1H and 19F nuclear magnetic resonance spectroscopy and imaging studies of fluvastatin？ in Lescol？ XL tablets in a USP-IV dissolution cell. J. Control. Release 2011, 156, 345–354, doi:10.1016/j.jconrel.2011.08.039.
[18]
Chen, Y.Y.; Hughes, L.P.; Gladden, L.F.; Mantle, M.D. Quantitative ultra-fast MRI of HPMC swelling and dissolution. J. Pharm. Sci. 2010, 99, 3462–3472.
[19]
Ho, L.; Mueller, R.; Krueger, C.; Gordon, K.C.; Kleinebudde, P.; Pepper, M.; Rades, T.; Shen, Y.; Taday, P.F.; Zeitler, J.A. Investigating dissolution performance critical areas on coated tablets: A case study using terahertz pulsed imaging. J. Pharm. Sci. 2010, 99, 392–402, doi:10.1002/jps.21845.
[20]
Russe, I.S.; Brock, D.; Knop, K.; Kleinebudde, P.; Zeitler, J.A. Validation of terahertz coating thickness measurements using X-ray microtomography. Mol. Pharm. 2012, 9, 3551–3559, doi:10.1021/mp300383y.
[21]
May, R.K.; Evans, M.J.; Zhong, S.; Warr, I.; Gladden, L.F.; Shen, Y.; Zeitler, J.A. Terahertz in-line sensor for direct coating thickness measurement of individual tablets during film coating in real-time. J. Pharm. Sci. 2011, 100, 1535–1544, doi:10.1002/jps.22359.
[22]
Zeitler, J.A.; Shen, Y.; Baker, C.; Taday, P.F.; Pepper, M.; Rades, T. Analysis of coating structures and interfaces in solid oral dosage forms by three dimensional terahertz pulsed imaging. J. Pharm. Sci. 2007, 96, 330–340, doi:10.1002/jps.20789.
[23]
McGinity, J.; Felton, L. Aqueous Polymeric Coatings for Pharmaceutical Dosage Forms; Informa Healthcare: London, UK, 2008.
[24]
Gendre, C.; Genty, M.; Silva, J.C.D.; Tfayli, A.; Boiret, M.; Lecoq, O.; Baron, M.; Chaminade, P.; Péan, J.M. Comprehensive study of dynamic curing effect on tablet coating structure. Eur. J. Pharm. Biopharm. 2012, 81, 657–665, doi:10.1016/j.ejpb.2012.04.006.
[25]
Palermo, R.; Cogdill, R.; Short, S.; Drennen Iii, J.; Taday, P.F. Density mapping and chemical component calibration development of four-component compacts via terahertz pulsed imaging. J. Pharm. Biomed. Anal. 2008, 46, 36–44, doi:10.1016/j.jpba.2007.10.023.
[26]
May, R.K.; Su, K.; Han, L.; Zhong, S.; Elliott, J.A.; Gladden, L.F.; Evans, M.; Shen, Y.; Zeitler, J.A. Hardness and density distributions of pharmaceutical tablets measured by terahertz pulsed imaging. J. Pharm. Sci. 2013, 102, 2179–2186, doi:10.1002/jps.23560.
Nazzal, S.; Khan, M.A. Controlled release of a self-emulsifying formulation from a tablet dosage form: Stability assessment and optimization of some processing parameters. Int. J. Pharm. 2006, 315, 110–121, doi:10.1016/j.ijpharm.2006.02.019.
[29]
Castellanos Gil, E.; Iraizoz Colarte, A.; Lara Sampedro, J.L.; Bataille, B. Subcoating with Kollidon VA 64 as water barrier in a new combined native dextran/HPMC–cetyl alcohol controlled release tablet. Eur. J. Pharm. Biopharm. 2008, 69, 303–311.
