title: Statistical Analysis of a Method to Predict Drug-Polymer Miscibility.
abstract: In this study, a method proposed to predict drug-polymer 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 drug-polymer 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 drug-polymer 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.
authors.forename: Matthias Manne
authors.initials: MM
authors.lastname: Knopp
authors.forename: Niels Erik
authors.initials: NE
authors.lastname: Olesen
authors.forename: Yanbin
authors.initials: Y
authors.lastname: Huang
authors.forename: René
authors.initials: R
authors.lastname: Holm
authors.forename: Thomas
authors.initials: T
authors.lastname: Rades
mesh_terms: D000465:Algorithms; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D015736:Felodipine / Q000737:chemistry; D016014:Linear Models; D008962:Models, Theoretical; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D011237:Predictive Value of Tests; D012995:Solubility; D013696:Temperature; D013816:Thermodynamics
chemical_list: D004364:Pharmaceutical Preparations; D011108:Polymers; D015736:Felodipine