Synergistic effect of SrTiO3/CuFe2O4/MIL-101(Co) as a MOF composite under Gamma-rays for antimicrobial potential versus bacteria and pathogenic fungi.

The primary emphasis of this study was on the innovative and scientifically valuable hydrothermal synthesis of MIL-101(Co) as a metal-organic framework (MOF) material. Subsequently, the CuFe2O4 was incorporated into the MOF by a reduction-precipitation technique. The SrTiO3/CuFe2O4/MIL-101(Co) composite was synthesized by using hydrothermal in situ growth process. The XRD and FESEM investigations of the SrTiO3/CuFe2O4/MIL-101(Co) composite definitively verified its crystalline structure and proved its production with exact shape and dimensions. The data indicated that Candida albicans displayed the greatest vulnerability to all three produced materials, with reported Minimum Inhibitory Concentration (MIC) values of 500 µg mL-1 for MIL-101(Co). The CuFe2O4/MIL-101(Co) compound, when produced, exhibits MIC values of 200 µg mL-1. Additionally, the combination of CuFe2O4/MIL-101(Co) with SrTiO3, shows MIC values of 50 µg mL-1. The results also indicated that the MIC values for MIL-101(Co), and CuFe2O4/MIL-101(Co) against S. aureus were 100 µg mL-1. Ultimately, SrTiO3/CuFe2O4/MIL-101(Co) exhibited identical MIC values of 50 µg mL-1 against S. aureus. The concentration of the bacterial protein was increased by adding MIL-101(Co), CuFe2O4/MIL-101(Co), and SrTiO3/CuFe2O4/MIL-101(Co). The antibacterial capabilities of the SrTiO3/CuFe2O4/MIL-101(Co) were increased after being subjected to gamma doses of 100.0 kGy. This process paves a ways for manufacturing innovation in near future.

Study on Acute Toxicity of Amiodarone New Complexes With Cyclodextrin.

Amiodarone low solubility and high permeability is the limiting step for its bioavailability, therefore new formulations are needed to improve the solubility of amiodarone either to increase its oral bioavailability or to reduce its toxic effects. Complexation of amiodarone with cyclodextrin results in improved dissolution rate, solubility, and allows for a more controlled drug release. We characterized the acute toxicity of a new amiodarone 2-hydroxypropyl-ß-cyclodextrin complex (AMD/HP-ß-CD) as powdered form and as a matrix based on Kollidon® and chitosan, administered intraperitoneally in laboratory animals. There were developed two formulations of matrix: one containing only pure AMD as a control sample (Fc) and one containing the inclusion complex with the optimal solubility (F). AMD was equitoxic with HP-ß-CD after intraperitoneal administration (289.4 mg/kg for AMD and 298.3 mg/kg for AMD/HP-ß-CD), with corresponding histopathological changes. The matrix based formulations presented higher LD50 values for acute toxicity, of 347.5 mg/kg for Fc and 455.6 mg/kg for F10, conducting to the idea of a safer administration because KOL and CHT matrix modified the solubility and controlled the AMD release. The LD50 is 1.5 higher for AMD/HP-ß-CD included in a KOL and CHT based matrix compared to the pure AMD, administered intraperitoneally.

Estimation of the In Vivo Release of Amiodarone From the Pharmacokinetics of Its Active Metabolite and Correlation With Its In Vitro Release.

Due to its very low water solubility and complex pharmacokinetics, a reliable point-to-point correlation of its in vitro release with its pharmacokinetics has not been achieved so far with amiodarone. The correlation of the in vitro dissolution of a drug with the pharmacokinetics of one of its metabolites was recently proposed by the authors of the article as an additional or alternative analysis to the usual in vitro correlations in vivo, mainly in the case of fast-absorbing drugs that have metabolites with a significant therapeutic effect. The model proposed by the authors considers that amiodarone has a slow dissolution, rapid absorption, and rapid metabolism, and before returning to the blood from other compartments, its pharmacokinetics is determined mainly by the kinetics of release in the intestine from the pharmaceutical formulation. Under these conditions, the rate of apparition of desethylamiodarone in the blood is a metric of the release of amiodarone in the intestinal fluid. Furthermore, it has been shown that such an estimated in vivo dissolution is similar, after time scaling, to the dissolution measured experimentally in vitro. Dissolution data of amiodarone and the pharmacokinetic data of its active metabolite desethylamiodarone were obtained in a bioequivalence study of 24 healthy volunteers. The elimination constant of the metabolite from plasma was estimated as the slope of the linear regression of logarithmically transformed data on the tail of plasma levels. Because the elimination of desethylamiodarone was shown to follow a monoexponential model, a Nelson-Wagner-type mass equilibrium model could be applied to calculate the time course of the "plasma metabolite fraction." After Levi-type time scaling for imposing the in vitro-in vivo correlation, the problem became that of the correlation between in vitro dissolution time and in vivo dissolution time, which was proven to follow a square root model. To validate the model, evaluations were performed for the reference drug and test drug separately. In both cases, the scaled time for in vivo dissolution, t*, depended approximately linearly on the square root of the in vitro dissolution time t, with the two regression lines being practically parallel.