Intra-tablet coating variability for several pharmaceutical tablet shapes
Intra-tablet coating variability for several pharmaceutical tablet shapes
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DOI：
10.1016/j.ces.2011.02.052
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发表时间：
2011-06
影响因子：
4.7
通讯作者：
Ben J. Freireich;W. Ketterhagen;C. Wassgren
中科院分区：
文献类型：
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作者：
Ben J. Freireich;W. Ketterhagen;C. Wassgren
采用离散单元法（DEM）-蒙特卡罗模拟相结合的算法，研究了6种片剂形状的片内包衣厚度变异性。DEM模拟用于收集片剂进入指定喷雾区时的片剂方向。蒙特卡洛模拟用于“包衣”片剂，假设均匀喷雾和从DEM模拟生成的分布中随机选择的方向。模拟结果表明，对于此处研究的非球形片剂形状，使用变异系数定义的包衣厚度变异性随包衣试验次数的平方根降低，然后接近渐近值。片剂的优选取向程度越大，渐近变异系数越大。此外，达到该渐近线所需的试验次数对于较大的渐近线值减少。这些发现与理论分析是一致的。对于研究的参数范围，增加锅速度降低了渐近变异系数，但增加填充水平没有一致的效果。渐近变异系数与片剂球形度、纵横比或条带与片剂面积比无关，但结果表明，片剂对称性的测量可能会提供更好的结果。改变包衣喷雾的角度，使每次包衣试验期间带的较大部分被包衣，与喷雾垂直于片剂床表面时相比，可获得较小的渐近变异系数。此外，当喷雾方向改变时，具有最小渐近变异系数的片剂的相对顺序改变。
A combined discrete element method (DEM)–Monte Carlo simulation algorithm is used to investigate intra-tablet coating thickness variability for six pharmaceutical tablet shapes. The DEM simulations are used to collect tablet orientations when the tablets enter a specified spray zone. The Monte Carlo simulations are used to “coat” the tablets assuming a uniform spray and orientations chosen randomly from the distribution generated by the DEM simulations. The simulations demonstrate that for the non-spherical tablet shapes investigated here, the coating thickness variability, defined using a coefficient of variation, decreases with the square root of the number of coating trials, then approaches an asymptotic value. The greater the degree of a tablet's preferred orientation, the larger the asymptotic coefficient of variation. In addition, the number of trials required to reach this asymptote decreases for larger asymptotic values. These findings are consistent with theoretical analyses. For the range of parameters investigated, increasing the pan speed decreases the asymptotic coefficient of variation, but increasing the fill level had no consistent effect. The asymptotic coefficients of variation did not correlate with tablet sphericity, aspect ratio, or band-to-tablet area ratio, but the results suggest that a measure of a tablet's symmetry may provide better results. Modifying the angle of the coating spray so that a larger portion of the band is coated during each coating trial results in smaller asymptotic coefficients of variation than when the spray is oriented normal to the tablet bed surface. In addition, the relative order of the tablets with the smallest asymptotic coefficients of variation changes when the spray orientation is changed.