Local Structural Effects Due to Micronization and Amorphization on an HIV Treatment Active Pharmaceutical Ingredient.

Processing procedures for inducing domain size reduction and/or amorphous phase generation can be crucial for enhancing the bioavailability of active pharmaceutical ingredients (APIs). It is important to quantify these reduced coherence phases and to detect and characterize associated structural changes, to ensure that no deleterious effects on safety, function, or stability occur. Here, X-ray powder diffraction (XRPD), total scattering pair distribution function (TSPDF) analysis, and solid-state nuclear magnetic resonance spectroscopy (SSNMR) have been performed on samples of GSK2838232B, an investigational drug for the treatment of human immunodeficiency virus (HIV).

Quantification of surface amorphous content using dispersive surface energy: the concept of effective amorphous surface area.

We investigate the use of dispersive surface energy in quantifying surface amorphous content, and the concept of effective amorphous surface area is introduced. An equation is introduced employing the linear combination of surface area normalized square root dispersive surface energy terms. This equation is effective in generating calibration curves when crystalline and amorphous references are used.

Using thermally stimulated current (TSC) to investigate disorder in micronized drug substance produced at different milling energies.

Purpose: To investigate the use of thermally stimulated current (TSC) to characterize disorder resulting from micronization of a crystalline drug substance. Samples processed at different milling energies are characterized, and annealing studied.

Methods: Molecular mobility in micronized drug substance was studied using TSC and compared to results from differential scanning calorimetry (DSC).

Reversed-phase membrane inlet mass spectrometry applied to the real-time monitoring of low molecular weight alcohols in chloroform.

Reversed-phase membrane inlet mass spectrometry incorporating a hollow-fiber Nafion membrane has been evaluated for the determination of low molecular weight alcohols in chloroform. The hydrophilic Nafion membrane preferentially transports methanol and ethanol, allowing percentage concentrations of the alcohols to be determined in a chloroform matrix. A linear response was observed for ethanol over the working range 0.