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以片剂薄膜包衣为例,研究不同优化参数对引导式进化模拟退火(GESA)优化效果的影响。

Effect of varying optimization parameters on optimization by guided evolutionary simulated annealing (GESA) using a tablet film coat as an example formulation.

作者信息

Plumb A Philip, Rowe Raymond C, York Peter, Doherty Christopher

机构信息

Pharmaceutical and Analytical R&D, AstraZeneca R&D Charnwood, Bakewell Road, Leicestershire LE11 5RH, Loughborough, UK.

出版信息

Eur J Pharm Sci. 2003 Mar;18(3-4):259-66. doi: 10.1016/s0928-0987(03)00016-2.

DOI:10.1016/s0928-0987(03)00016-2
PMID:12659937
Abstract

The purpose of this study was to investigate the effect of varying optimization parameters on the proposed optimum of a tablet coating formulation requiring minimization of crack velocity and maximization of film opacity. An artificial neural network (ANN) comprising six input and two output nodes separated by a single hidden layer of five nodes was trained using 100 pseudo-randomly distributed records and optimized by guided evolutionary simulated annealing (GESA). GESA was unable to identify a formulation that satisfied both a crack velocity of 0 ms(-1) and a film opacity of 100% due to conflict centred on the response of the properties to variation in pigment particle size. Constraining film thickness exacerbated the property conflict. By adjusting property weights (i.e. the relative importance of each property), GESA was able to propose formulations that were either crack resistant or that were fully opaque. Reducing the stringency of the performance criteria (crack velocity >0 ms(-1), film opacity <100%) enabled GESA to propose optima that met or exceeded the looser targets. Under these conditions, starting GESA from different locations within model space resulted in the proposal of different optima. Therefore, application of loose targets resulted in the identification of an optimal zone within which all formulations satisfied these less stringent performance criteria. It is concluded that application of the most stringent performance criteria and selection of appropriate property weights is necessary for unequivocal identification of the true optimum. A strategy for optimization experiments is proposed.

摘要

本研究的目的是调查不同优化参数对一种片剂包衣配方的建议最优值的影响,该配方要求使裂纹速度最小化并使薄膜不透明度最大化。一个人工神经网络(ANN)由六个输入节点和两个输出节点组成,中间隔着一个包含五个节点的单隐藏层,使用100个伪随机分布的记录进行训练,并通过引导进化模拟退火(GESA)进行优化。由于围绕颜料粒径变化时性能响应的冲突,GESA无法识别出一种既满足裂纹速度为0 ms⁻¹又满足薄膜不透明度为100%的配方。限制薄膜厚度加剧了性能冲突。通过调整性能权重(即每个性能的相对重要性),GESA能够提出抗裂或完全不透明的配方。降低性能标准的严格程度(裂纹速度>0 ms⁻¹,薄膜不透明度<100%)使GESA能够提出达到或超过较宽松目标的最优值。在这些条件下,从模型空间内的不同位置启动GESA会导致提出不同的最优值。因此,应用宽松目标导致识别出一个最优区域,在该区域内所有配方都满足这些不太严格的性能标准。得出的结论是,应用最严格的性能标准并选择合适的性能权重对于明确识别真正的最优值是必要的。提出了一种优化实验策略。

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