Impact of surfactants on solution behavior and membrane transport of amorphous solid dispersions.

The purpose of the study was to develop an amorphous solid dispersion (ASD) of a poorly soluble compound (AK100) and investigate the impact of different surfactants on its dissolution, supersaturation and membrane transport. The solubility of the AK100 was determined in crystalline and amorphous form in the absence and presence of three surfactants at different concentrations: sodium dodecyl sulphate (SDS), polysorbate 80 (PS80) and D-α-tocopherol polyethylene glycol succinate (TPGS). The relation between solubility and surfactant solubilization was evaluated using a computational model.

Excipient effects on supersaturation, particle size dynamics, and thermodynamic activity of multidrug amorphous formulations.

Multidrug formulations enhance patient compliance and extend the life cycle of pharmaceutical products. To overcome solubility challenges for multidrug combinations, amorphous formulations are commonly used. However, the excipients for creating amorphous formulations are often selected without an understanding of their effects on the bioavailability of the drugs.

Potential Use of Supercharging Agents for Improved Mass Spectrometric Analysis of Monoclonal Antibodies and Antibody-Drug Conjugates.

The addition of supercharging (SC) reagents in electrospray ionization coupled mass spectrometry (ESI-MS) has demonstrated several advantages for protein analysis such as reduced required mass range of the instrument, narrowed charge-state distribution, increased sensitivity, and adduct suppression. The potential use of SC reagents to improve analyses of larger and complex protein molecules such as monoclonal antibodies and antibody-drug conjugates (ADCs) has not been previously reported. In this study, the effect of seven SC reagents (-nitrobenzyl alcohol (-NBA), dimethyl sulfoxide (DMSO), -nitroanisole (-NA), propane sultone (PS), ethylene carbonate (EC), propylene carbonate (PC), and sulfolane) on ESI-MS acquired spectra of deglycosylated, intact, and reduced trastuzumab and a vcMMAE-trastuzumab ADC was investigated under denaturing conditions.

Investigating the Impact of Sample Preparation on Mass Spectrometry-Based Drug-To-Antibody Ratio Determination for Cysteine- and Lysine-Linked Antibody-Drug Conjugates.

Antibody-drug conjugates (ADCs) are heterogeneous biotherapeutics and differ vastly in their physicochemical properties depending on their design. The number of small drug molecules covalently attached to each antibody molecule is commonly referred to as the drug-to-antibody ratio (DAR). Established analytical protocols for mass spectrometry (MS)-investigation of antibodies and ADCs often require sample treatment such as desalting or interchain disulfide bond reduction prior to analysis.

Magnetic Beads for Desalting of Monoclonal Antibodies and Antibody-Drug Conjugates.

Characterization of antibody-drug conjugates (ADCs) using mass spectrometry (MS) is important in drug discovery and formulation development and as part of the quality control processes. To facilitate electrospray ionization (ESI) and produce high-quality mass spectra, common components of storage solutions for monoclonal antibodies (mAbs) and ADCs, such as nonvolatile phosphate-buffered saline (PBS), should be replaced before analysis. Centrifugal spin-type kits are extensively used for the desalting or buffer-exchange of mAbs and ADCs samples.

Application of triple quadrupole mass spectrometry for the characterization of antibody-drug conjugates.

Antibody-drug conjugates (ADCs) are an inherently heterogeneous class of biotherapeutics, the development of which requires extensive characterization throughout. During the earliest phases of preclinical development, when synthetic routes towards the desired conjugate are being assessed, the main interest lies in the determination of the average drug-to-antibody ratio (DAR) of a given batch as well as information about different conjugation species. There has been a trend in mass spectrometry (MS)-based characterization of ADCs towards the use of high-resolving mass spectrometry for many of these analyses.

Effect of increased milking frequency and residual milk removal on milk production and milk fatty acid composition in lactating cows.

It has been well established that milk yield is affected both by milking frequency and due to the removal of residual milk, but the influence of a combination of these factors is unclear. In this study, four mid-lactation cows were used in a 4 × 4 Latin square design to test the hypothesis that the effects of more frequent milking and residual milk removal on milk yield and composition are additive and alter milk fatty acid composition. Treatments comprised two or four times daily milking in combination with (or without) residual milk removal over a 96 h interval preceded by a 2 d pretreatment period and followed by a 8 d washout in each 14 d experimental period.