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Application of a sensorial response model to the design of an oral liquid pharmaceutical dosage form.

机译:感觉反应模型在口服液体药物剂型设计中的应用。

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In this paper, we discuss the application of a compartmental model to study the sensorial response, in terms of taste intensity versus time, in an oral solution for pharmaceutical use. The numerical model was developed from sensorial response curves obtained by a panel of three trained individuals. Parameter identification was carried out by means of a least-squares procedure that obtained the linear coefficients in the model by solving an exact linear least-squares problem conditional on the values of the nonlinear parameters for each iteration. Thus, nonlinear estimation was done in terms of the first-order kinetic parameters only, and ill-conditioning of the Hessian matrix present in these models was solved. Results of modeling for a set of formulations were used to determine the effects of various ingredients (sweeteners and an essence) on a baseline unflavored formulation of acetaminophen in a mixture of cosolvents. The first moment of the area under the curve of taste intensity versus time was found to be the best global indicator of taste for the purpose of product design. It was found that a mixture of sweeteners and an essence was the most efficient way of masking the bitter taste of this active ingredient.
机译:在本文中,我们讨论了隔室模型的应用,以研究口感浓度随时间变化的药用口服溶液的感官反应。该数值模型是根据由三个受过训练的人员组成的小组获得的感觉反应曲线开发的。通过最小二乘法进行参数识别,该过程通过求解每次迭代的非线性参数值来求解精确的线性最小二乘问题,从而获得模型中的线性系数。因此,仅根据一阶动力学参数进行了非线性估计,并且解决了这些模型中存在的Hessian矩阵的不良情况。一组制剂的建模结果用于确定各种成分(甜味剂和香精)对助溶剂混合物中对乙酰氨基酚的基线无味制剂的影响。为了产品设计的目的,发现口味强度随时间变化曲线下面积的第一时刻是最佳的总体口味指标。发现甜味剂和香精的混合物是掩盖该活性成分苦味的最有效方法。

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