Drug Absorption Modeling as a Tool to Define the Strategy in Clinical Formulation Development

The purpose of this mini review is to discuss the use of physiologically-based drug absorption modeling to guide the formulation development. Following an introduction to drug absorption modeling, this article focuses on the preclinical formulation development. Case studies are presented, where the emphasis is not only the prediction of absolute exposure values, but also their change with altered input values. Sensitivity analysis of technologically relevant parameters, like the drug’s particle size, dose and solubility, is presented as the basis to define the clinical formulation strategy. Taking the concept even one step further, the article shows how the entire design space for drug absorption can be constructed. This most accurate prediction level is mainly foreseen once clinical data is available and an example is provided using mefenamic acid as a model drug. Physiologically-based modeling is expected to be more often used by formulators in the future. It has the potential to become an indispensable tool to guide the formulation development of challenging drugs, which will help minimize both risks and costs of formulation development

Efficiency of Coagulation/Flocculation for the Removal of Complex Mixture of Textile Fibers from Water

Synthetic fibers enter wastewater treatment plants together with natural fibers, which may affect treatment efficiency, a fact not considered in previous studies. Therefore, the aim of the present study was to evaluate the efficiency of the coagulation/flocculation process for the removal of a mixture of textile fibers from different water matrices. Natural and synthetic fibers (100 mg/L; cotton, polyacrylonitrile, and polyamide) were added to a synthetic matrix, surface water and laundry wastewater and subjected to coagulation/flocculation experiments with ferric chloride (FeCl3) and polyaluminum chloride (PACl) under laboratory conditions. In the synthetic matrix, both coagulants were found to be effective, with FeCl3 having a lesser advantage, removing textile fibers almost completely from the water (up to 99% at a concentration of 3.94 mM). In surface water, all dosages had approximately similar high values, with the coagulant resulting in complete removal. In laundry effluent, the presence of surfactants is thought to affect coagulation efficiency. PACl was found to be effective in removing textile fibers from laundry wastewater, with the lowest removal efficiency being 89% and all dosages having similar removal efficiencies. Natural organic matter and bicarbonates showed a positive effect on the efficiency of FeCl3 in removing textile fibers from surface water. PACl showed better performance in coagulating laundry wastewater while surfactants had a negative effect on FeCl3 coagulation efficiency

Investigation of biological activities and secondary metabolites of hydnum repandum acetone extract

© 2019, Romanian Society for Pharmaceutical Sciences. All rights reserved. This study aimed to evaluate the biological activities and polyphenolic contents of the acetone extract of H. repandum mushroom. Polyphenolic compounds were evaluated by high-performance liquid chromatography (HPLC). The antioxidant activity was assessed by radical scavenging activity assays and reducing power. The antimicrobial activity was established based on the values of the minimum inhibitory concentration (MIC) using microdilution method. Cytotoxic activity was determined by 3-4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT). The genotoxic and antimutagenic activities were tested using cytokinesis block micronucleus (CBMN) assay on human peripheral blood lymphocytes in vitro. Among the determined polyphenolic compounds, ferulic acid and quercetin were mostly found. The extract showed high free radical scavenging activity, while the reducing power was less emphasized and concentration-dependent. The MIC fluctuated in a range of 0.009-10 mg/mL. The cytotoxic activity (based on IC50) ranged from 116.5 to 158.33 µg/mL, when HeLa cells were the most sensitive. The highest tested concentrations of the extract showed significant genotoxic activity, while against mitomycin C, the extract caused protective activity. The results indicated that H. repandum acetone extract contained secondary metabolites which showed biological activities such as antioxidant, antimicrobial, cytotoxic, genotoxic and protective against chemotherapeutics, indicating that their inclusion in nutrition could be of great importance in the prevention and treatment of various pathological conditions

Automatic image-to-world registration based on x-ray projections in cone-beam CT-guided interventions

Intraoperative imaging offers a means to account for morphological changes occurring during the procedure and resolve geometric uncertainties via integration with a surgical navigation system. Such integration requires registration of the image and world reference frames, conventionally a time consuming, error-prone manual process. This work presents a method of automatic image-to-world registration of intraoperative cone-beam computed tomography (CBCT) and an optical tracking system. Multimodality (MM) markers consisting of an infrared (IR) reflective sphere with a 2 mm tungsten sphere (BB) placed precisely at the center were designed to permit automatic detection in both the image and tracking (world) reference frames. Image localization is performed by intensity thresholding and pattern matching directly in 2D projections acquired in each CBCT scan, with 3D image coordinates computed using backprojection and accounting for C-arm geometric calibration. The IR tracking system localized MM markers in the world reference frame, and the image-to-world registration was computed by rigid point matching of image and tracker point sets. The accuracy and reproducibility of the automatic registration technique were compared to conventional (manual) registration using a variety of marker configurations suitable to neurosurgery (markers fixed to cranium) and head and neck surgery (markers suspended on a subcranial frame). The automatic technique exhibited subvoxel marker localization accuracy (<0.8 mm) for all marker configurations. The fiducial registration error of the automatic technique was (0.35±0.01) mm, compared to (0.64±0.07 mm) for the manual technique, indicating improved accuracy and reproducibility. The target registration error (TRE) averaged over all configurations was 1.14 mm for the automatic technique, compared to 1.29 mm for the manual in accuracy, although the difference was not statistically significant (p=0.3). A statistically significant improvement in precision was observed—specifically, the standard deviation in TRE was 0.2 mm for the automatic technique versus 0.34 mm for the manual technique (p=0.001). The projection-based automatic registration technique demonstrates accuracy and reproducibility equivalent or superior to the conventional manual technique for both neurosurgical and head and neck marker configurations. Use of this method with C-arm CBCT eliminates the burden of manual registration on surgical workflow by providing automatic registration of surgical tracking in 3D images within ∼20 s of acquisition, with registration automatically updated with each CBCT scan. The automatic registration method is undergoing integration in ongoing clinical trials of intraoperative CBCT-guided head and neck surgery

Apoptosis and genome instability in children with autoimmune diseases

© 2018 The Author(s). As apoptosis and genome instability in children with autoimmune diseases (AIDs) are insufficiently investigated, we aimed to analyse them in peripheral blood lymphocytes (PBLs) of children and adolescents with Hashimoto's thyroiditis (HT), Graves' disease (GD) and type 1 diabetes mellitus (T1DM), including possible factors that could affect their occurrence. The study population included 24 patients and 19 healthy controls. Apoptotic cells were detected using an Annexin V-FITC/7-AAD kit. Genome instability was measured as micronuclei (MNs) frequency using the cytokinesis-block MN assay. In addition, comet assay was performed for determination of genome instability as genome damage index (GDI) in new subpopulation of patients with T1DM. The percentage of apoptotic PBLs in patients with AID was significantly lower than in control subjects. There was a positive correlation between thyroid-stimulating homone (TSH) concentration and the proportion of cells in late stage apoptosis in patients with autoimmune thyroid diseases (AITDs). The MN frequency in patients was significantly higher than in controls. Individuals with HT or T1DM had a significantly higher MN frequency than those with GD. Similarly, the value of GDI in patients with T1DM was significantly higher than in controls. The level of apoptosis was positively correlated with MN frequency as well as with GDI in patients with AID. In conclusion, children with AITD (HT and GD) and T1DM have a significantly lower level of apoptosis in PBLs and significantly higher MN frequency as GDI than healthy subjects. Apoptosis and the level of genome instability in these patients with AID are positively correlated