Antikainen Osmo, Kachrimanis Kyriakos, Malamataris Stavros, Yliruusi Jouko, Sandler Niklas
Division of Pharmaceutical Technology, Faculty of Pharmacy, University of Helsinki, Finland.
J Pharm Pharmacol. 2007 Jan;59(1):51-7. doi: 10.1211/jpp.59.1.0007.
A biologically inspired spiking neural network model, the pulse coupled neural network (PCNN), has been applied for the first time in bulk particle characterization, and specifically in the characterization of pharmaceutical granule size distributions. The PCNN was trained on surface images of pharmaceutical granule beds, and the adjustable parameters (radius neuron interconnection, r0, linking weight coefficient, beta, local threshold potential, VTheta, and number of iterations) were successfully optimized using design of experiments. As demonstrated with size fractions of granules, it was found that the PCNN produced granule size-dependent signals. In general, a first highest and relatively narrow peak located in the region of two to twelve iterations corresponded to smaller particle size, while larger particles resulted in wider peaks and in highest (not first) peak at a range between 13 and 25 iterations. Better predictions, i.e. lower RMSEP (root mean squared error of prediction) values, were obtained using high beta value, low r0 and VTheta values, while the number of iterations had to exceed 110 and the optimized model (RMSEP lower than 5) corresponded to PCNN variables: r0=1, beta=0.4, VTheta=2, and number of iterations=150. The coefficient of determination (R2) of the model was 0.94 and the predicted variation (Q2) was 0.91, while the Pearson correlation coefficient between the predicted and the measured mean particle size by sieving for eight test batches was 0.98. These findings could be characterized as promising and encouraging for the further use of image analysis by PCNNs in pharmaceutical bulk particle size and shape characterization.
一种受生物启发的脉冲神经网络模型,即脉冲耦合神经网络(PCNN),首次被应用于散装颗粒表征,特别是在药物颗粒尺寸分布的表征中。PCNN在药物颗粒床的表面图像上进行训练,并使用实验设计成功优化了可调参数(半径神经元互连,r0,连接权重系数,β,局部阈值电位,VTheta,以及迭代次数)。通过颗粒的尺寸分级表明,发现PCNN产生了与颗粒尺寸相关的信号。一般来说,位于两到十二次迭代区域内的第一个最高且相对较窄的峰值对应较小的颗粒尺寸,而较大的颗粒则导致更宽的峰值以及在13到25次迭代范围内的最高(非第一个)峰值。使用高β值、低r0和VTheta值可获得更好的预测,即更低的RMSEP(预测均方根误差)值,而迭代次数必须超过110,优化后的模型(RMSEP低于5)对应于PCNN变量:r0 = 1,β = 0.4,VTheta = 2,以及迭代次数 = 150。该模型的决定系数(R2)为0.94,预测变异(Q2)为0.91,而通过筛分对八个测试批次预测的平均粒径与测量的平均粒径之间的皮尔逊相关系数为0.98。这些发现对于PCNN在药物散装颗粒尺寸和形状表征中进一步使用图像分析而言,可以说是有前景且令人鼓舞的。