Automated Non-Sterile Pharmacy Compounding: A Multi-Site Study in European Hospital and Community Pharmacies with Pediatric Immediate Release Propranolol Hydrochloride Tablets.

Pharmacy compounding, the art and science of preparing customized medications to meet individual patient needs, is on the verge of transformation. Traditional methods of compounding often involve manual and time-consuming processes, presenting challenges in terms of consistency, dosage accuracy, quality control, contamination, and scalability. However, the emergence of cutting-edge technologies has paved a way for a new era for pharmacy compounding, promising to redefine the way medications are prepared and delivered as pharmacy-tailored personalized medicines. In this multi-site study, more than 30 hospitals and community pharmacies from eight countries in Europe utilized a novel automated dosing approach inspired by 3D printing for the compounding of non-sterile propranolol hydrochloride tablets. CuraBlend <sup>®</sup> excipient base, a GMP-manufactured excipient base (pharma-ink) intended for automated compounding applications, was used. A standardized study protocol to test the automated dosing of tablets with variable weights was performed in all participating pharmacies in four different iterative phases. Integrated quality control was performed with an in-process scale and NIR spectroscopy supported by HPLC content uniformity measurements. In total, 6088 propranolol tablets were produced at different locations during this study. It was shown that the dosing accuracy of the process increased from about 90% to 100% from Phase 1 to Phase 4 by making improvements to the formulation and the hardware solutions. The results indicate that through this automated and quality controlled compounding approach, extemporaneous pharmacy manufacturing can take a giant leap forward towards automation and digital manufacture of dosage forms in hospital pharmacies and compounding pharmacies

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

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