Issue link: https://www.e-digitaleditions.com/i/316458
38 May 2014 Tablets & Capsules Croscarmellose sodium manufac- turers emphasize that the excipient can be used to manufacture tablets by either direct compression or wet granulation. If wet granulation is used, it is recommended that you add a portion of the croscarmellose sodi - um during granulation so that it will remain within the granules (intra- granular); add the remaining portion to the final blend so it resides outside the granules (extra-granular). This extra-granular portion will promote the disintegration of the tablet and the intra-granular portion will pro- mote the disintegration of the gran- ules. The graph in Figure 4 compares the dissolution time of methyldopa tablets in which the croscarmellose sodium was added as intra- and extra- granules to those that received only extra-granular croscarmellose sodium. As Table 1 shows, the first tablet con- tained 1 percent of both intra- and extra-granular croscarmellose sodium, while the second contained 2 percent of an extra-granular addition only. Figure 2 Molecular structure of croscarmellose sodium n H H CH 2 H O O H H H H O OH OH CH 2 0CH 2 COONa OH H H OH H O H H CH 2 0CH 2 COONa H O O H H H H O O OH CH 2 0CH 2 COONa OH H H OH H O O O O CH 2 CH 2 Figure 3 Croscarmellose sodium as seen through a scanning electron microscope Figure 4 Comparison of dissolution times of methyldopa tablets to which croscarmellose sodium was added during and after wet granulation (intra- and extra-granular addition) to tablets to which croscarmellose sodium was added afterward (extra- granular addition only) 100 80 60 40 20 0 0 Time (min) Release (%) 5 10 20 Intra and extra Extra only Table 1 Constituents and use levels in methyldopa tablets compared in Figure 4 Intra- and extra-granular Extra-granular only Intra-granular Extra-granular Intra-granular Extra-granular additions (%) additions (%) additions (%) additions (%) Methyldopa 38.47 38.47 Microcrystalline cellulose 101 55.53 55.53 Croscarmellose sodium (intra-granular) 1.00 PVP K-30 3.00 3.00 Croscarmellose sodium (extra-granular) 1.00 2.00 Magnesium stearate 1.00 1.00 Total 100.00 100.00 * All with average tablet weight of 650 milligrams and hardness of 6 kilopascal j-EOE_36-41_Masters 5/14/14 10:18 AM Page 38