School of Pharmacy, University of Otago, Dunedin, New Zealand; Cavendish Laboratories, University of Cambridge, Cambridge, United Kingdom; TeraView Ltd., Cambridge, United Kingdom.
Int J Pharm. 2013 Dec 5;457(2):521-6. doi: 10.1016/j.ijpharm.2013.05.039. Epub 2013 May 27.
Terahertz pulsed imaging (TPI) was employed to explore its suitability for detecting differences in the film coating thickness and drug layer uniformity of multilayered, sustained-release coated, standard size pellets (approximately 1mm in diameter). Pellets consisting of a sugar starter core and a metoprolol succinate layer were coated with a Kollicoat(®) SR:Kollicoat(®) IR polymer blend for different times giving three groups of pellets (batches I, II and III), each with a different coating thickness according to weight gain. Ten pellets from each batch were mapped individually to evaluate the coating thickness and drug layer thickness between batches, between pellets within each batch, and across individual pellets (uniformity). From the terahertz waveform the terahertz electric field peak strength (TEFPS) was used to define a circular area (approximately 0.13 mm(2)) in the TPI maps, where no signal distortion was found due to pellet curvature in the measurement set-up used. The average coating thicknesses were 46 μm, 71 μm and 114 μm, for batches I, II and III respectively, whilst no drug layer thickness difference between batches was observed. No statistically significant differences in the average coating thickness and drug layer thickness within batches (between pellets) but high thickness variability across individual pellets was observed. These results were confirmed by scanning electron microscopy (SEM). The coating thickness results correlated with the subsequent drug release behaviour. The fastest drug release was obtained from batch I with the lowest coating thickness and the slowest from batch III with the highest coating thickness. In conclusion, TPI is suitable for detailed, non-destructive evaluation of film coating and drug layer thicknesses in multilayered standard size pellets.
太赫兹脉冲成像（TPI）被用于探索其在检测多层、缓释包衣、标准大小丸剂（直径约 1 毫米）的包衣厚度和药物层均匀性差异方面的适用性。丸剂由糖起始核心和琥珀酸美托洛尔层组成，用 Kollicoat（®）SR：Kollicoat（®）IR 聚合物混合物包衣不同时间，得到三组丸剂（批 I、II 和 III），根据增重，每组具有不同的包衣厚度。从每个批次中取出 10 个丸剂进行单独映射，以评估批次之间、每个批次内的丸剂之间以及单个丸剂之间的包衣厚度和药物层厚度（均匀性）。从太赫兹波形中，使用太赫兹电场峰值强度（TEFPS）来定义 TPI 图谱中的圆形区域（约 0.13 毫米（2）），在使用的测量设置中，由于丸剂曲率，不会发现信号失真。平均包衣厚度分别为批 I、II 和 III 的 46 μm、71 μm 和 114 μm，而批之间未观察到药物层厚度差异。在批次内（丸剂之间），平均包衣厚度和药物层厚度没有统计学上的显著差异，但在单个丸剂之间观察到厚度变化很大。这些结果通过扫描电子显微镜（SEM）得到证实。包衣厚度结果与随后的药物释放行为相关。最快的药物释放来自具有最低包衣厚度的批 I，最慢的来自具有最高包衣厚度的批 III。总之，TPI 适用于多层标准大小丸剂的包衣和药物层厚度的详细、非破坏性评估。
