One strategy for improving the dissolution of poorly water soluble drugs is to prepare solid dispersions such as binary mixtures with hydrophilic carriers. These mixtures are generally characterized by better solubility than those of the individual components from which they are formed. In the present study, solid dispersions of ketoconazole (KET) with Pluronic F127 (PLU) were prepared by the grinding method. Solid–liquid equilibria in the system being studied were investigated by differential scanning calorimetry. A phase diagram for the whole range of compositions was constructed. The investigation revealed that ketoconazole and Pluronic F127 form a simple eutectic system containing 4.4 % w/w of ketoconazole at the eutectic point. The results of Fourier transform infrared spectroscopy and X-ray powder diffractometry studies of obtained mixtures suggest that there is no drug-carrier interaction and both components are crystalline in the solid dispersion with the whole range of composition. The prepared mixtures show an appreciable improvement of the dissolution rate of KET in 0.5 % w/v sodium lauryl sulfate. The improvement of the dissolution rate of drug is additionally increased by effective solubilization.

Background Metabolic syndrome (MetS) is a complex metabolic disease connected especially with lipid and carbohydrate disturbances. It is postulated that oxidative stress (OS) is linked to metabolic syndrome, constituting a novel component of its pathogenesis. Aim We aimed to examine the plasma level of oxidatively modified proteins––advanced oxidation protein products (AOPP) and ischemia modified albumin (IMA)––as well as thiol (SH) groups and evaluate their connection with metabolic agents in relation to MetS prevalence. Subjects and methods The levels of AOPP, IMA and SH groups were measured spectrophotometrically in 106 patients with MetS risk factors and in 32 control subjects. Results The levels of examined parameters differed significantly between patients with MetS risk factors and the control group. AOPP significantly correlated with glucose (r = 0.30, p = 0.008), HDL-Ch (r = −0.34, p = 0.005), TG (r = 0.48, p < 0.001) and fibrinogen (r = 0.37, p < 0.001). The levels of AOPP and IMA increased progressively with the number of MetS risk factors, being the most significant for AOPP. The highest values of AOPP were associated with the presence of at least three risk factors. Only AOPP were an independent determinant for MetS occurrence in the studied population (OR = 2.72, p = 0.04). Mutual dependence between metabolic, oxidative stress and inflammatory parameters was revealed. Conclusions Oxidative modifications of proteins are increased in MetS and accumulation of MetS risk factors enhances manifestation of OS. AOPP is the most appropriate parameter for determination of OS, with potential diagnostic value in MetS patients.

The objective of the present investigation was to study the effect of eutectic formation on in vitro dissolution of simvastatin (SIM) released from mixtures with acetylsalicylic acid (ASA) prepared by a grinding method. SIM–ASA mixtures were characterized by means of differential scanning calorimetry (DSC), infrared spectroscopy (IR), X-ray powder diffractometry (XRPD), and in vitro dissolution tests. IR spectroscopy and XRPD studies indicated no interaction between SIM and ASA in the solid state. The DSC investigation has revealed that SIM and ASA form a simple eutectic system containing 66.6 % w/w of SIM at the eutectic point. In vitro dissolution studies of SIM and its mixtures with ASA were carried out. The eutectic mixture shows an appreciable increase in the dissolution rate in comparison with other ratios and SIM in 0.5 % w/v sodium lauryl sulfate. The dissolution enhancement of SIM was related to the effective wetting of the drug particles with a significantly reduced size released from eutectic composition. In conclusion, dissolution of SIM can be enhanced through eutectic formation with ASA by means of simple mechanical activation (a grinding method).

The pathophysiological role of human chitinases and chitinase-like proteins (CLPs) is not fully understood. We aimed to determine the levels of neutrophil-derived chitotriosidase (CHIT1), acidic mammalian chitinase (AMCase) and chitinase 3-like protein 1 (YKL-40) in patients with type 2 diabetes (T2D) and verify their association with metabolic and clinical conditions of these patients. Neutrophils were obtained from the whole blood by gradient density centrifugation from 94 T2D patients and 40 control subjects. The activities of CHIT1 and AMCase as well as leukocyte elastase (LE) were measured fluorometrically and concentration of YKL-40 immunoenzymatically. Also, routine laboratory parameters in serum/plasma were determined by standard methods. The levels of all three examined proteins were about 2-times higher in diabetic patients in comparison to control subjects. They were significantly correlated with the activity of LE and increased progressively across tertiles of LE activity. Moreover, the activities of CHIT1 and AMCase were significantly correlated with each other. Metabolic compensation of diabetes did not influence the levels of these proteins. In the subgroup of patients with inflammatory evidence only YKL-40 concentration was significantly higher compared to those without inflammation. The highest levels of all three proteins were observed in patients with macroangiopathies. Insulin therapy was associated with lower levels of examined proteins. We revealed that neutrophils may be an important source of the increased levels of chitinases and CLPs in T2D, and these proteins may participate in inflammatory mechanisms in the course of the disease and consequent development of diabetic angiopathies.

Introduction: Chitotriosidase (CHIT1) is a chitinolytic enzyme involved mainly in the immune and inflammatory response. It shows increased activity in many pathologies, including in newly diagnosed type 2 diabetes (T2D). This study aimed to investigate this enzyme’s activity in plasma of...