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Coamorphous salt in a 1:1 ratio prepared by ball milling from Fluvastatin sodium (FLV) and Pioglitazone hydrochloride (PGZ·HCl) can be selectively formed by neat grinding (NG). Furthermore, the salt–cocrystal continuum was preferably formed by employing liquid-assisted grinding (LAG) using ethanol (EtOH). Attempts to prepare the coamorphous salt starting from the salt–cocrystal continuum by NG were unsuccessful. Interestingly, through ball milling by NG or LAG, a great diversity of solid forms (PGZ·HCl-FLV 1:1) could be accessed: NG and hexane (coamorphous); ethyl acetate (physical mixture); EtOH (salt–cocrystal continuum); and water (which presents two Tg, indicating immiscibility of the components). An exploration was performed at different drug-to-drug ratios by NG. By differential scanning calorimetry (DSC), the presence of two endothermic events was observed in this screening: incongruous melting point (solidus) and excess of one of the components (liquidus), except in the 1:1 solid form. From these results, eutectic behavior was observed. Through the construction of a binary phase diagram, it was determined that the 1:1 molar ratio gives rise to the formation of the most stable coamorphous composition. Dissolution profile studies of these solid forms were carried out, specifically on pure FLV and the solid forms of PGZ⋅HCl-FLV (1:2; 1:4; and 1:6), together with the coamorphous 1:1 salt. By itself, pure FLV presented the highest Kint (13.6270 ± 0.8127 mg/cm2⋅min). On the other hand, the coamorphous 1:1 showed a very low Kint (0.0220 ± 0.0014 mg/cm2·min), indicating very fast recrystallization by the FLV, which avoids observing a sudden release of this drug in the solution. This same behavior was observed in the eutectic composition 1:2. In the other solid forms, the value of Kint increases along with the %w of FLV. From the mechanochemical point of view, ball milling by NG or LAG became an important synthetic tool since it allows obtaining a great variety of solid forms to explore the solid-state reactivity of the drug–drug solid-form PGZ HCl-FLV. [ABSTRACT FROM AUTHOR]

Ball-milling using neat grinding (NG) or liquid-assisted grinding (LAG) by varying the polarity of the solvents allowed access to various drug–drug solid forms of pioglitazone hydrochloride (PGZ·HCl) and rosuvastatin calcium (RSV). Using NG, the coamorphous form was formed from the reaction of pioglitazone hydrochloride (PGZ·HCl) and rosuvastatin calcium (RSV) in a 2:1 molar ratio. The formation of the expected coamorphous salt could not be corroborated by FT-IR, but DSC data showed that it was indeed a single-phase amorphous mixture. By varying the molar ratios of the reactants, either keeping PGZ·HCl constant and varying RSV or vice versa, another coamorphous form was obtained when a 1:1 molar ratio was employed. In the case of the other outcomes, it was observed that they were a mixture of solid forms coexisting simultaneously with the coamorphous forms (1:1 or 2:1) together with the drug that was in excess. When RSV was in excess, it was in an amorphous form. In the case of PGZ·HCl, it was found in a semicrystalline form. The intrinsic dissolution rates (IDRs) of the solid forms of PGZ·HCl-RSV in stoichiometric ratios (1:1, 2:1, 1:4, 6:1, and 1:10) were evaluated. Interestingly, a synchronized release of both drugs in the dissolution medium was observed. In the case of the release of RSV, there were no improvements in the dissolution profiles, because the acidic media caused the formation of degradation products, limiting any probable modification in the dissolution processes. However, the coamorphous 2:1 form exhibited an improvement of 1.03 times with respect to pure PGZ·HCl. It is proposed that the modification of the dissolution process of the coamorphous 2:1 form was limited by changes in the pH of the media as RSV consumes protons from the media due to degradation processes. [ABSTRACT FROM AUTHOR]

The study aimed to investigate the effects of pioglitazone hydrochloride (PGZ) and resveratrol (RES) on yellow-feathered broiler chickens. A total of 500 broiler chickens were randomly divided into four groups and fed a basic diet (control group) or a basic diet supplemented with 15 mg/kg PGZ, 400 mg/kg RES, or 15 mg/kg PGZ plus 400 mg/kg RES for 28 days. Compared with the control group, the PGZ and PGZ plus RES groups presented a significantly higher average daily gain and a decreased feed-to-gain ratio. Increases in the dressing percentage, semi-eviscerated yield, muscle intramuscular fat content, and C18:1n-9c, C18:3n-6, C20:3n-3, and monounsaturated fatty acid (MUFA) percentages were found in the PGZ plus RES group. Moreover, the diet supplemented with RES or PGZ plus RES increased the activities of catalase, glutathione peroxidase, and superoxide dismutase, and decreased the levels of reactive oxygen species of thigh muscle. Additionally, the mRNA abundance of peroxisome proliferator-activated receptor γ coactivator 1α, fatty acid-binding protein 3, nuclear factor erythroid-2-related factor 2, and superoxide dismutase 1 was increased in the PGZ plus RES group. In conclusion, this study suggested that dietary supplementation of PGZ combined with RES improved the growth performance, the muscle intramuscular fat content, and antioxidant ability of yellow-feathered broiler chickens. [ABSTRACT FROM AUTHOR]

Pioglitazone, a popular antidiabetic drug, which was recently shown to be effective in the treatment of skin ulcers, was successfully encapsulated in polysaccharide nanoparticles and used as a bioactive component of the wound-dressing material based on modified bacterial nanocellulose. Alginate and hydroxypropyl cellulose were used as a matrix for the nanoparticulate drug-delivery system. The matrix composition and particles' size, as well as drug encapsulation efficiency and loading, were optimized. Pioglitazone hydrochloride (PIO) loaded particles were coated with chitosan introduced into the crosslinking medium, and covalently attached to the surface of bacterial nanocellulose functionalized with carboxyl groups. PIO was released from the surface of the hybrid material in a controlled manner for 5 days. Preliminary cytotoxicity studies confirmed safety of the system at PIO concentrations as high as 20 mg/mL. The obtained hybrid system may have potential application in the treatment of skin ulcers e.g., in diabetic foot. [ABSTRACT FROM AUTHOR]