title: Application of chemometric methods to differential scanning calorimeter (DSC) to estimate nimodipine polymorphs from cosolvent system.
abstract: The focus of this study was to evaluate the applicability of chemometrics to differential scanning calorimetry data (DSC) to evaluate nimodipine polymorphs. Multivariate calibration models were built using DSC data from known mixtures of the nimodipine modification. The linear baseline correction treatment of data was used to reduce dispersion in thermograms. Principal component analysis of the treated and untreated data explained 96% and 89% of the data variability, respectively. Score and loading plots correlated variability between samples with change in proportion of nimodipine modifications. The R(2) for principal component regression (PCR) and partial lease square regression (PLS) were found to be 0.91 and 0.92. The root mean square of standard error of the treated samples for calibration and validation in PCR and PLS was found to be lower than the untreated sample. These models were applied to samples recrystallized from a cosolvent system, which indicated different proportion of modifications in the mixtures than those obtained by placing samples under different storage conditions. The model was able to predict the nimodipine modifications with known margin of error. Therefore, these models can be used as a quality control tool to expediently determine the nimodipine modification in an unknown mixture.
authors.affiliation: Division of Product Quality Research, Office of Testing and Research, OPS, CDER, FDA, Silver Spring , MD , USA.
authors.forename: Akhtar
authors.initials: A
authors.lastname: Siddiqui
authors.forename: Ziyaur
authors.initials: Z
authors.lastname: Rahman
authors.forename: Mansoor A
authors.initials: MA
authors.lastname: Khan
mesh_terms: D002138:Calibration; D002152:Calorimetry, Differential Scanning / Q000379:methods*; D003460:Crystallization; D016018:Least-Squares Analysis; D008956:Models, Chemical; D009553:Nimodipine / Q000737:chemistry*; D025341:Principal Component Analysis; D011786:Quality Control; D012997:Solvents / Q000737:chemistry*
chemical_list: D012997:Solvents; D009553:Nimodipine
keywords: Chemometrics; DSC; PCS; PLS; nimodipine; polymorphs