Influence of eutectic mixture as a multi-component system in the improvement of physicomechanical and pharmacokinetic properties of diacerein

Formulation of Diacerein Cocrystal Using β-Resorcylic Acid for Improvement of Physicomechanical and Biopharmaceutical Properties

“…DIA (Figure A) showed characteristic peaks at 2θ values of 10.4°, 17.4°, and 27.9° . RA (Figure B) revealed the characteristic intense peaks at 2θ values of 13.5°, 26.8°, and 28.4° . The appearance of a new and distinct diffraction pattern with peaks at 2θ values at 12.2°, 18.5°, and 19.9° with decreased intensity were observed in the DIA–RA system.…”

“…DIA is an enthralling drug molecule containing potential functional groups like −COOH, −C–O–C–, and −COOC–, which have a significant role in the field of crystal engineering. In the previous research on cocrystallization of DIA, the practical use of mechanochemical methods has received special attention. , Additionally, our previous research obtained a newly developed eutectic between DIA and RA (1:3) via the liquid-assisted grinding method . According to the previous research, the possibility of antisolvent cocrystallization to design cocrystals is worthy of discussion .…”

“…This problem was resolved through the addition of a small quantity of 2% w/w microcrystalline cellulose-102 (MCC) as a binder to each sample. To understand the compaction behavior, the resulting powders were compressed under different forces ranging from 1 to 9 tons (9.8 × 10 3 to 88.26 × 10 3 N) with a dwell time of 1 min . Before the compaction process, the die and punch were lubricated using a dispersion of magnesium stearate in acetone (1% w/v). , Heckel analysis expresses the compression behavior of the powder under pressure following first-order kinetics, as shown in eq : where D is the relative density of the compact (i.e., the ratio of the compact density to the true density), 1 – D is the porosity (ε) of the powder, P is the applied pressure, and K (the slope) and A (the y intercept) are the Heckel constants calculated from the Heckel plot (a graph of ln­[1/(1 – D )] vs P ).…”

“…The mean yield pressure ( P y ) is given by K = 1/ P y , and A denotes the densification at low pressure. The yield strength (σ 0 ), which demonstrates the powder characteristics during deformation or fragmentation, is calculated as σ 0 = (3 K ) −1 . , Here the true densities were measured as mass per unit volume of the compact at the highest applied force in tons …”

“…The raw DIA and prepared sample were suspended in 0.2% w/v sodium carboxymethylcellulose and administered through oral gavage. Each animal was treated with a DIA dose equivalent to 30 mg/kg of body weight, respectively. , Blood samples were collected from the retro-orbital venous plexus of the rats at different time points (0, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 12, and 24 h). The plasma samples were harvested by centrifugation at 10 000 rpm for 20 min and frozen at −20 °C until determination; see section S1 in the Supporting Information (SI) for the plasma sample preparation and method.…”