Chemometrical aspects of quality in pharmaceutical technology:the application of robustness criteria and multi criteria decision making in optimization procedures for pharmaceutical formulations

摘要

In pharmaceutical technology one is often engaged with the design and analysis of formulations. A formulation of a solid dosage form is normally a mixture of components. This formulation usually consists of a number of components with fixed concentrations like the the medicinal substance(s) (drug), the lubricant, the glidant, possibly the disintegrant and components with variable concentrations like the fillerbinders. In the case of tablets, several physical demands can be set to the formulation like having certain (minimum or maximum) values for the crushing strength, the disintegration time, the friability, the weight variation, content uniformity, etc. The desired properties should be reached by changing the concentrations of the filler-binders, sometimes the disintegrant and/or by changing the manufacturing conditions. Another important property of a formulation is to keep the desired values of the physical demands as constant as possible during production or shelf-life despite (small) variations in the manufacturing conditions or in the concentrations of the components. In other words the fomulation should ideally be robust against the mentioned sources of error or a certain quality level should be maintained. This thesis considers only the mixture optimization part (changing filler-binderldisintegrant concentrations) of the formulation optimization and robustness against errors in the mixture concentration settings.