Two-Stage Plasma-Thermal Nitridation Processes for the Production of Aluminum Nitride Powders from Aluminum Powders.

The synthesis of aluminum nitride (AlN) powders is traditionally done via the thermal nitridation process, in which the reaction temperature reaches as high as 960 °C, with more than several hours of reaction time. Moreover, the occurrence of agglomeration in melting Al particles results in poor AlN quality and a low efficiency of nitridation. In this study, an atmosphere-pressure microwave-plasma preceded the pre-synthesis process. This process operates at 550 °C for 2⁻10 min with the addition of NH4Cl (Al: NH4Cl = 1:1) for generating a hard AlN shell to avoid the flow and aggregation of the melting Al metals. Then, the mass production of AlN powders by the thermal nitridation process can be carried out by rapidly elevating the reaction temperature (heating rate of 15 °C/min) until 1050 °C is reached. X-Ray Diffractometer (XRD) crystal analysis shows that without the peak, Al metals can be observed by synthesizing AlN via plasma nitridation (at 550 °C for 2 min, Al: NH4Cl = 1:1), followed by thermal nitridation (at 950 °C for 1 h). Moreover, SEM images show that well-dispersed AlN powders without agglomeration were produced. Additionally, the particle size of the produced AlN powder (usually < 1 µm) tends to be reduced from 2⁻5 µm (Al powders), resulting in a more efficient synthesizing process (lower reaction temperature, shorter reaction time) for mass production.

Pharmacokinetic characterization of BMS-936561, an anti-CD70 antibody-drug conjugate, in preclinical animal species and prediction of its pharmacokinetics in humans.

CD70 is a tumor necrosis factor (TNF)-like type II integral membrane protein that is transiently expressed on activated T- and B-lymphocytes. Aberrant expression of CD70 was identified in both solid tumors and haematologic malignancies. BMS-936561 (αCD70_MED-A) is an antibody-drug conjugate composed of a fully human anti-CD70 monoclonal antibody (αCD70) conjugated with a duocarmycin derivative, MED-A, through a maleimide-containing citrulline-valine dipeptide linker. MED-A is a carbamate prodrug that is activated by carboxylesterase to its active form, MED-B, to exert its DNA alkylation activity. In vitro serum stability studies suggested the efficiencies of hydrolyzing the carbamate-protecting group in αCD70_MED-A followed a rank order of mouse>rat > >monkey>dog~human. Pharmacokinetics of αCD70_MED-A was evaluated in mice, monkeys, and dogs after single intravenous doses. In mice, αCD70_MED-A was cleared rapidly, with no detectable exposures after 15 min following dosing. In contrast, αCD70_MED-A was much more stable in monkeys and dogs. The clearance of αCD70_MED-A in monkeys was 58 mL/d/kg, ~2-fold faster than that in dogs (31 mL/d/kg). The human PK profiles of the total αCD70 and αCD70_MED-A were predicted using allometrically scaled monkeys PK parameters of αCD70 and the carbamate hydrolysis rate constant estimated in dogs. Comparing the predicted and observed human PK from the phase I study, the dose-normalized concentration-time profiles of αCD70_MED-A and the total αCD70 were largely within the 5(th)-95(th) percentile of the predicted profiles.

An integrated multiplatform bioanalytical strategy for antibody-drug conjugates: a novel case study.

BACKGROUND: The bioanalytical strategy for antibody-drug conjugates (ADC) includes numerous measurements integrally designed to provide comprehensive characterization of PK, PD and immunogenicity. This manuscript describes the utilization of reagents specifically tailored to an ADC with a microtubule polymerization inhibitor payload and cathepsin B cleavable linker. METHODS: The PK strategy includes the evaluation of physiological levels of total antibody, active ADC, total ADC, antibody-conjugated payload and unconjugated payload. These data are evaluated in the context of target and antidrug antibody levels to elucidate bioactive ADC. RESULTS & CONCLUSION: Herein, we discuss how this strategy has been applied and present our preliminary observations. Continuously evolving to meet pipeline demands, the integrated bioanalytical data will provide critical insights into the exposure-response relationship.