Development of a Pure Certified Reference Material of D-Mannitol

Abstract

A new certified reference material (CRM) of D-mannitol (GBW(E) 100681) has been developed in this study. We describe the preparation, structure determination, characterization, homogeneity study, stability study, as well as uncertainty estimation. The main component was 99.91% ± 0.01%. The moisture content of the candidate CRM was 0.036% ± 0.002%, as measured by Karl Fischer titration. The nonvolatile and volatile impurities in the candidate CRM were all much less than 0.01%, which was determined by the ICP–MS and headspace GC–FID methods, respectively. The purity of the D-mannitol CRM was 99.9% ± 1.1% (k = 2), as measured by the two independent approaches involving the mass balance method (MB) and quantitative nuclear magnetic resonance technique (qNMR). The D-mannitol CRM was stable during the monitoring period for each temperature. It is stable for up to 48 months at room temperature and 28 days at 50 °C. The uncertainty was evaluated by combining the contributions from characterization, homogeneity, and stability. The developed D-mannitol CRM would effectively support method validation and proficiency testing, as well as effectively guarantee the accuracy, reliability, and comparability of results.

Compatibility study of mirtazapine with several excipients used in pharmaceutical dosage forms employing thermal and non-thermal methods

“…It is documented in scientific literature that the suspicion of drug-excipient interactions arises from significant shifts of the DSC melting signal as well as the modification of the enthalpy value associated with the melting process of the API [33][34][35]. A definite conclusion cannot be drawn however from the sole interpretation of the DSC curves, an incompatibility assessment requiring correlations between the results obtained using multiple techniques, among others thermal analysis and IR spectroscopy [36].…”

“…2e) than the ones seen previously for the discussed mixtures, an expected occurrence considering the structural particularities of aerosil. As such, the most intense spectral signals can be attributed to the excipient and are determined by the presence of the Si-O bond [36] (max. at 1074 cm −1 ).…”