Statistical Analysis of a Method to Predict Drug-Polymer Miscibility

Matthias Manne Knopp, Niels Erik Olesen, Yanbin Huang, René Holm, Thomas Rades

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    In this study, a method proposed to predict drugepolymer miscibility from differential scanning calorimetry measurements was subjected to statistical analysis. The method is relatively fast and inexpensive and has gained popularity as a result of the increasing interest in the formulation of drugs as amorphous solid dispersions. However, it does not include a standard statistical assessment of the experimental uncertainty by means of a confidence interval. In addition, it applies a routine mathematical operation known as “transformation to linearity,” which previously has been shown to be subject to a substantial bias. The statistical analysis performed in this present study revealed that the mathematical procedure associated with the method is not only biased, but also too uncertain to predict drugepolymer miscibility at room temperature. Consequently, the statistical inference based on the mathematical procedure is problematic and may foster uncritical and misguiding interpretations. From a statistical perspective, the drugepolymer miscibility prediction should instead be examined by deriving an objective function, which results in the unbiased, minimum variance properties of the least-square estimator as provided in this study.
    TidsskriftJournal of Pharmaceutical Sciences
    Udgave nummer1
    Sider (fra-til)362-367
    Antal sider6
    StatusUdgivet - 2016

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