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Screening and Preparation of Cocrystals: A Comparative Study of Mechanochemistry vs Slurry Methods.

ABSTRACT: Cocrystals of biologically active molecular compounds have potential utility in drug products thanks to their effect upon physicochemical properties such as aqueous solubility. The fact that control of cocrystallization can be more challenging than crystallization of single-component crystals means that systematic studies that address the methodology of cocrystal screening, production, and purification are a topical subject. We previously reported a comparison of slow evaporation vs mechanochemistry for a library of 25 molecular cocrystals. Herein, we compare the previously reported mechanochemistry results (solvent-drop grinding (SDG) with eight solvents) with new results obtained from slurrying in five preferred solvents using the same library of 25 cocrystals. Overall, both methods were found to be effective with slurrying and SDG being 94 and 78.5% successful, respectively. Importantly, 96% of the cocrystals formed via slurrying were observed to be free of starting materials (coformers) according to powder X-ray diffraction (PXRD), whereas this was the case for only 72% of the cocrystals prepared by SDG. Slurrying therefore compared favorably with mechanochemistry, which tends to leave small amounts of unreacted coformer(s) as byproducts, and solution crystallization, which often affords crystals of the least soluble coformer because it can be difficult to control the saturation of three or more solids. Perhaps the most interesting and surprising result of this study was that water slurrying proved to be highly effective, even for low-solubility coformers. Indeed, water slurrying was found to be effective for 21 of the 25 cocrystals studied.

SUBMITTER: Haskins MM

PROVIDER: S-EPMC8273892 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundA number of orbital diseases may be evaluated based on the degree of exophthalmos, but there is still no gold standard method for the measurement of this parameter. In this study we compare two exophthalmometry measurement methods (digital photography and clinical) with regard to reproducibility and the level of correlation and agreement with measurements obtained with Computerized Tomography (CT) measurements.MethodsSeventeen patients with bilateral proptosis and 15 patients with normal orbits diseases were enrolled. Patients underwent orbital CT, Hertel exophthalmometry (HE) and standardized frontal and side facial photographs by a single trained photographer. Exophthalmometry measurements with HE, the digital photographs and axial CT scans were obtained twice by the same examiner and once by another examiner. Pearson correlation coefficient (PCC) was used to assess correlations between methods. Validity between methods was assessed by mean differences, interintraclass correlation coefficients (ICC's), and Bland-Altman plots.ResultsMean values were significantly higher in the proptosis group (34 orbits) than in the normal group (30 orbits), regardless of the method. Within each group, mean digital exophthalmometry measurements (24.32 ± 5.17 mm and 18.62 ± 3.87 mm) were significantly greater than HE measurements (20.87 ± 2.53 mm and 17.52 ± 2.67 mm) with broader range of standard deviation. Inter-/intraclass correlation coefficients were 0.95/0.93 for clinical, 0.92/0.74 for digital, and 0.91/0.95 for CT measurements. Correlation coefficients between HE and CT scan measurements in both groups of subjects (r = 0.84 and r = 0.91, p < 0.05) were greater than those between digital and CT scan measurements (r = 0.61 and r = 0.75, p < 0.05). On the Bland-Altman plots, HE showed better agreement to CT measurements compared to the digital photograph method in both groups studied.ConclusionsAlthough photographic digital exophthalmometry showed strong correlation and agreement with CT scan measurements, it still performs worse than and is not as accurate as clinical Hertel exophthalmometry. This trail is registered with NCT01999790.

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Screening and Preparation of Cocrystals: A Comparative Study of Mechanochemistry vs Slurry Methods.

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