No abstract

In this study, hyperspectral imaging (HSI) sensor was used to rapidly estimate the content of an active pharmaceutical ingredient (API) in powder blend samples in order to optimize small molecule formulation. Small molecule powder blend samples containing excipients and varying API concentrations were prepared using a blender. The spectrum of each powder blend was obtained using a short‐wave infrared hyperspectral imaging (SWIR HSI) system over a wavelength range of 1,000–2,500 nm. The use of the SWIR HSI method to predict API concentration in the powder blend samples was validated against that of a high‐performance liquid chromatography method. Partial least squares (PLS) regression and least squares support vector machine (LS‐SVM) analyses were used to build calibration models for predicting API concentration in the powder samples. Both the PLS and LS‐SVM models yielded high coefficients of determination of 0.99 and low errors (root‐mean‐square error of prediction) for API content prediction, which were 0.73 and 0.60 mg, respectively. Furthermore, image processing algorithms were developed to visualize the predicted API concentration in each pixel of the powder surface. Concentration map and binary images were also used to visualize the API concentration in the powder samples. The results suggest that the HSI technique permits the quantification and visualization of pharmaceutical ingredients and could be easily used during manufacturing for the non‐destructive formulations optimization and quality control of products.

We report the crystallization of a metastable small-molecule solvate and the effect of the isolation method on the physical and material properties of the resulting anhydrous material. The anhydrous crystalline products obtained from two different isolation routes using either a temperature-driven form change or a solvent-wash-mediated form change were analyzed by a suite of material-sparing characterization methods probing both physical form and material properties such as particle size distribution and powder flow behavior. The temperature-driven desolvation method was found to be time-consuming and undesirable. A relatively rapid desolvation approach was obtained using an ethyl acetate wash-mediated process. However, this method leads to powder with a broader particle size distribution, poorer flowability, higher interparticulate friction, and lower bulk density compared with the powder obtained by the temperature-driven desolvation process. The direct impact of the method of isolation on the material properties of the drug substance highlights the importance of not only understanding the crystallization process and form landscape but also the ability to implement systematic characterization to identify key powder properties of drug candidates early in the drug development process.