Impact of Drug-Polymer Interaction in Amorphous Solid Dispersion Aiming for the Supersaturation of Poorly Soluble Drug in Biorelevant Medium.

The aim of this study was to investigate the influence of the production method and the polymeric carrier on the ability to generate and maintain the supersaturation of a poorly soluble drug in biorelevant medium. The amorphous solid dispersion of sulfamethoxazole, an antibacterial drug, was produced using two different polymers by spray-drying or hot melt extrusion methods. When Eudragit EPO was used, supersaturation was maintained up to 24 h for both techniques at all drug-polymer proportions. However, when Soluplus was employed in hot melt extrusion, a smaller amount of drug was dissolved when compared to the amorphous drug. The proportion of 3:7 drug-Eudragit EPO (w/w) produced by spray-drying presented a higher amount of drug dissolved in supersaturation studies and it was able to maintain the physical stability under different storage conditions throughout the 90-day evaluation. Supersaturation generation and system stability were found to be related to more effective chemical interaction between the polymer and the drug provided by the production method, as revealed by the 1D ROESY NMR experiment. Investigation of drug-polymer interaction is critical in supersaturating drug delivery systems to avoid crystallization of the drug and to predict the effectiveness of the system. Chemical compounds studied in this article: Sulfamethoxazole (PubChem CID: 4539) and Methacrylate copolymer - Eudragit EPO (PubChem CID: 65358).

4'-Hydroxy-6,7-methylenedioxy-3-methoxyflavone: A novel flavonoid from Dulacia egleri with potential inhibitory activity against cathepsins B and L.

A new flavone, 4'-hydroxy-6,7-methylenedioxy-3-methoxyflavone 1, and two other nucleosides, ribavirin 2 and adenosine 3, were isolated from the leaves of Dulacia egleri. The nucleosides were identified by spectroscopic techniques (1D, 2D-NMR) while the structure of the flavonoid was established by 1D, 2D-NMR analysis, including HRESIMS data. The results obtained in the biological assays showed that the compound 1 was able to inhibit cathepsins B and L with IC50 of 14.88 ±â€¯0.18 µM and 3.19 ±â€¯0.07 µM, respectively. The mechanism of inhibition for both enzymes were determined showing to be competitive at cathepsin B with Ki = 12.8 ±â€¯0.6 µM and non-linear non-competitive with positive cooperativity inhibition at cathepsin L with Ki = 322 ±â€¯33 µM, αKi = 133 ±â€¯15 µM, ßKi = 5.14 ±â€¯0.41 µM and γKi = 13.2 ±â€¯13 µM.

Chemical constituents and antileukemic activity of Eugenia dysenterica.

The study about Eugenia dysenterica led to the isolation of 3-acetyl-urs-12-en-28-oic (1), 3-acetyl-olean-12-en-28-oic acid (2) and isoquercetin (3) from the stem barks, and of 3-O-ß-glucopyranosyl-ß-sitosterol (4), methyl 3-hydroxy-4-methoxybenzoate (5), methyl 4-hydroxyphenyl propionate (6), E-methyl-4-hydroxycinnamate (7), quercetin-3-O-(6ꞌꞌ-O-galloyl)-ß-d-glucopyranoside (8) and quercetin-3-O-ß-d-galactopyranoside (9) from the leaves. The structures 1-9 were set through the analysis of their NMR spectroscopic data. Compounds 2, 3 and 5-8 were reported for the first time in the Eugenia genus. Compound 8 reduced cell viability and presented IC50 values 40.3 and 36.7 µM, for the CCRF-CEM and the Kasumi-1 cells, respectively.