Structural, thermal, vibrational, solubility and DFT studies of a tolbutamide co-amorphous drug delivery system for treatment of diabetes.

Among the strategies for bioavailability improvement of poorly soluble drugs, co-amorphous systems have revealed to have a significant impact in the increase of the aqueous solubility of the drug, and at the same time increasing the amorphous state stability and dissolution rate when compared with the neat drug. Tolbutamide (TBM) is an oral hypoglycemic drug largely used in the treatment of type II Mellitus diabetes. TBM is a class II drug according to the Biopharmaceutical Classification System, meaning that it has low solubility and higher permeability. The aim of this study was to synthesize a co-amorphous material of tolbutamide (TBM) with tromethamine (TRIS). Density functional theory (DFT), allowed to study the structural, electronic, and thermodynamic properties, as well as solvation effects. In same theory level, several interactions tests were performed to obtain the most thermodynamically favorable drug-coformer intermolecular interactions. The vibrational spectra (mid infrared and Raman spectroscopy) are in accordance with the theoretical studies, showing that the main molecular interactions are due to the carbonyl, sulfonyl, and amide groups of TMB and the alcohol and amine groups of TRIS. X-ray powder diffraction was used to study the physical stability in dry condition at 25 °C of the co-amorphous system, indicating that the material remained in an amorphous state up to 90 days. Differential scanning calorimetry and thermogravimetric results showed a high increase of the Tg when compared with the amorphous neat drug, from 4.3 °C to 83.7 °C, which generally translated into good physical stability. Solubility studies demonstrated an increase in the solubility of TBM by 2.5 fold when compared with its crystalline counterpart.

Synthesis of a Glibenclamide Cocrystal: Full Spectroscopic and Thermal Characterization.

A cocrystal of glibenclamide, an antidiabetic drug classified as type II compound according to the Biopharmaceutics Classification System, has been synthesized using tromethamine as coformer in 1:1 molar ratio, by slow solvent evaporation cocrystalization. The cocrystal obtained was characterized by X-ray powder diffraction, differential scanning calorimetry, Raman, mid infrared, and near-infrared spectroscopy. The results consistently show the formation of a cocrystal between active pharmaceutical ingredients and conformer with the synthons corresponding to hydrogen bonding between hydrogen in amines of tromethamine and carbonyl and sulfonyl groups in glibenclamide.

A FT-NIR spectroscopy methodology to estimate firing distance based on the direct analysis of the bullet impact surface.

A new methodology to estimate firing distance based on the direct analysis of organic components of gunshot residues (GSRs) on the bullet impact surface using Fourier transform near-infrared (FT-NIR) spectroscopy is proposed. Mathematical models relating firing distance with spectral information were developed using data obtained from a series of shots performed with a Glock model 17C (114 mm barrel length and 9 × 19 mm cartridges) at different distances, from 20 to 90 cm, against a white 40 × 40 cm square cloth (70% polyester/30% cotton) target. The study was repeated with two different types of ammunition. Spectra were obtained around the bullet entrance hole at 4 perpendicular directions and at 5 radial distances in diffuse reflectance mode with the assistance of a fiber optic probe. Principal component analysis showed that FT-NIRS displayed sensitivity in the recognition of the differences between the GSRs from the two different types of ammunition. Partial least squares regression models allowed the estimation of firing distance for both types of ammunition. Prediction errors lower than 11 cm were obtained for shots up to 90 cm.

The role of L-arginine in inclusion complexes of omeprazole with cyclodextrins.

In this study, we investigate how the effect of L-arginine (ARG) and cyclodextrins upon omeprazole (OME) stability and solubility. The effect of the presence of ARG on the apparent stability constants (K(1:1)) of the inclusion complexes formed between OME and each cyclodextrin, beta-cyclodextrin (betaCD), and methyl-beta-cyclodextrin (MbetaCD) is studied by phase solubility diagrams and nuclear magnetic resonance (NMR) spectroscopy. The interaction of OME with those cyclodextrins, in the presence of ARG, is characterized using NMR spectroscopy and molecular dynamics simulations. ARG significantly increases the drug solubility and complex stability, in comparison to inclusion complexes formed in its absence. The effect is more pronounced for the OME:betaCD complex. ARG also contributes to a larger stability of OME when free in aqueous solution. The combination of ARG with cyclodextrins can represent an important tool to develop stable drug formulations.