Machinability of enamel under grinding process using diamond dental burrs.

Enamel grinding is a critical dental surgery process. However, tooth damage during the process remains a significant problem. Grinding forces, burr wear, and surface quality were characterised in relation to grinding speed, enamel orientation, grinding depth, and burr grit grain size. Results indicated that enamel rod orientation, grinding depth, and grinding speed critically affected enamel grinding. Occlusal surface grinding resulted in significantly higher normal forces, surface roughness, and marginally greater tangential forces than axial surface grinding. Damage to enamel machined surfaces indicated the significant impact of diamond grit size and rod orientation. Burr wear was primarily diamond grit peeling off and breakage. Surface roughness of axial and occlusal sections was largely influenced by grinding speed and diamond grit size. Improving the surface quality of machined enamel surfaces could be realised using fine burrs, reducing the grinding speed and grinding depth, and adjusting the feed direction vertical to the rod orientation. Enamel surface quality and roughness could be improved by reducing brittle failure and circular runout during the grinding process, respectively.

Solution degradant of mirabegron extended release tablets resulting from a Strecker-like reaction between mirabegron, minute amounts of hydrogen cyanide in acetonitrile, and formaldehyde in PEG during sample preparation.

During the related substances testing of mirabegron extended release tablets, an unknown peak was observed in HPLC chromatograms in a level exceeding the identification threshold. By using a strategy that combines LC-PDA/UV-MSn with mechanism-based stress studies, the unknown peak was rapidly identified as cyanomethyl mirabegron, a solution degradant that is caused by a Strecker-like reaction between the API, formaldehyde (an impurity in PEG), and HCN (an impurity in HPLC grade acetonitrile). The mechanism of the solution degradation chemistry was verified by stressing mirabegron with formaldehyde and trimethylsilyl cyanide (TMSCN, a synthetic reagent that generates HCN upon contact with water), in which the secondary amine group of mirabegron first reacts with formaldehyde to form the iminium ion intermediate; the latter then undergoes a nucleophilic attack by cyanide to yield the cyanomethyl mirabegron. The structure of the impurity was further confirmed through the synthesis of the impurity and subsequent structure characterization by 1D and 2D NMR. Due to the ubiquitous presence of formaldehyde in pharmaceutical excipients (e.g., PEG and polysorbate) and trace amount of HCN in HPLC grade acetonitrile, this type of solution degradation would likely occur in sample preparations of pharmaceutical finished products containing APIs with primary and secondary amine moieties. In a GMP environment, such an event may trigger undesirable out-of-specification (OOS) investigations; the results of this paper should help resolve such OOS investigations or even prevent these events from happening in the first place.