A cocrystal of the antihypertensive drug chlorthalidone (CTD) with caffeine (CAF) was obtained (CTD-CAF) by the slurry method, for which a 2:1 stoichiometric ratio was found by powder and single-crystal X-ray diffraction analysis. Cocrystal CTD-CAF showed a supramolecular organization in which CAF molecules are embedded in channels of a 3D network of CTD molecules. The advantage of the cocrystal in comparison to CTD is reflected in a threefold solubility increase and in the dose/solubility ratios, which diminished from near-unit values for D_0D to 0.29 for D_0CC. Furthermore, dissolution experiments under non-sink conditions showed improved performance of CTD-CAF compared with pure CTD. Subsequent studies showed that CTD-CAF cocrystals transform to CTD form I where CTD precipitation inhibition could be achieved in the presence of pre-dissolved polymer HPMC 80–120 cPs, maintaining supersaturation drug concentrations for at least 180 min. Finally, dissolution experiments under sink conditions unveiled that the CTD-CAF cocrystal induced, in pH-independent manner, faster and more complete CTD dissolution when compared to commercial tablets of CTD. Due to the stability and dissolution behavior of the novel CTD-CAF cocrystal, it could be used to develop solid dosage forms using a lower CTD dose to obtain the same therapeutic response and fewer adverse effects.

Background: Curcumin appears to be well tolerated and effective for managing chronic inflammatory pain, but its poor oral bioavailability has been a hurdle in its use as a therapeutic agent. The current study was performed to characterize a novel co-amorphous compound based on curcumin/L-arginine 1:2 (CAC12). Methods: Stability, solubility and structural characterization of the CAC12 were carried out by spectrometry techniques and in vitro assays, whereas the antinociceptive and anti-inflammatory effects were evaluated by CFA or carrageenan models. The mechanism of action was determined by cytokine quantification, and pharmacokinetic parameters were obtained through UPLC-MS/MS. The co-amorphous compound was prepared by fast solvent evaporation. Powder XRD, 13C-NMR, ATR-FTIR and TGA/DSC thermal analysis showed a 1:2 stoichiometry for the CAC12. Results: CAC12 was 1000 times more soluble than curcumin, and it was stable for 1 month at 40 °C and 75% relative humidity or for 60 min in physiological medium at pH 4.5–6.8. Co-amorphous curcumin/L-arginine, but not curcumin + L-arginine, decreased carrageenan- or CFA-induced inflammation and nociception by decreasing IL-1α, IL-1β, IL-6, TNF-α, MCP-1 and CXCL1 cytokines. The bioavailability of free plasmatic curcumin increased about 22.4 times when it was given as CAC12 relative to a phytosome formulation at the equivalent dose. Conclusions: Results suggest the possible use of CAC12 to treat inflammatory pain disorders in human beings.

Immobilization of enzymes has many advantages for their application in biotechnological processes. In particular, the cross-linked enzyme aggregates (CLEAs) allow the production of solid biocatalysts with a high enzymatic loading and the advantage of obtaining derivatives with high stability at low cost. The purpose of this study was to produce cross-linked enzymatic aggregates (CLEAs) of LipMatCCR11, a 43 kDa recombinant solvent-tolerant thermoalkaliphilic lipase from Geobacillus thermoleovorans CCR11. LipMatCCR11-CLEAs were prepared using (NH₄)₂SO₄ (40% w/v) as precipitant agent and glutaraldehyde (40 mM) as cross-linker, at pH 9, 20 °C. A U₁₀(5⁶) uniform design was used to optimize CLEA production, varying protein concentration, ammonium sulfate %, pH, glutaraldehyde concentration, temperature, and incubation time. The synthesized CLEAs were also analyzed using scanning electron microscopy (SEM) that showed individual particles of <1 µm grouped to form a superstructure. The cross-linked aggregates showed a maximum mass activity of 7750 U/g at 40 °C and pH 8 and retained more than 20% activity at 100 °C. Greater thermostability, resistance to alkaline conditions and the presence of organic solvents, and better durability during storage were observed for LipMatCCR11-CLEAs in comparison with the soluble enzyme. LipMatCCR11-CLEAs presented good reusability by conserving 40% of their initial activity after 9 cycles of reuse.

Background/Objective: In recent studies, it has been shown that dietary bioactive compounds can produce health benefits; however, it is not known whether an improvement in solubility can enhance their biological effects. Thus, the aim of this work was to study whether co-amorphous (CoA) naringenin or fisetin with enhanced solubility modify glucose and lipid metabolism, thermogenic capacity and gut microbiota in mice fed a high-fat, high-sucrose (HFSD) diet. Methods: Mice were fed with an HFSD with or without CoA-naringenin or CoA-fisetin for 3 months. Body weight, food intake, body composition, glucose tolerance, hepatic lipid composition and gut microbiota were assessed. Results: CoA-naringenin demonstrated significant reductions in fat-mass gain, improved cholesterol metabolism, and enhanced glucose tolerance. Mice treated with CoA-naringenin gained 45% less fat mass and exhibited improved hepatic lipid profiles, with significant reductions seen in liver triglycerides and cholesterol. Additionally, both CoA-flavonoids increased oxygen consumption (VO₂), contributing to enhanced energy expenditure and improved metabolic flexibility. Thermogenic activation, indicated by increased UCP1 and PGC-1α levels, was observed with CoA-fisetin, supporting its role in fat oxidation and adipocyte size reduction. Further, both CoA-flavonoids modulated gut microbiota, restoring diversity and promoting beneficial bacteria, such as Akkermansia muciniphila, which has been linked to improved metabolic health. Conclusions: These findings suggest that co-amorphous naringenin or fisetin offers promising applications in improving solubility, metabolic health, and thermogenesis, highlighting the potential of both as therapeutic agents against obesity and related disorders.