A family of new compounds with sulfonamide and amide functional groups as potential Alzheimer's disease drugs were prepared by multistep synthesis. Thermal stability measurements recorded the initial decomposition in the range of 200-220°C, close above the melting point. The final compounds were tested for their ability to inhibit acetylcholinesterase and butyrylcholinesterase, and the in vitro dissolution behavior of selected compounds was studied through both lipophilic and hydrophilic matrix tablets. All nine tested derivatives were even more active in inhibiting acetylcholinesterase than the clinically used rivastigmine. Regression analysis of the obtained dissolution profiles was performed, and the effects of the pH and the release mechanism were determined. Some substances showed remarkable biological activity and became a subject of interest for further extensive study.
- MeSH
- acetylcholinesterasa metabolismus MeSH
- Alzheimerova nemoc * farmakoterapie MeSH
- butyrylcholinesterasa * metabolismus MeSH
- cholinesterasové inhibitory * farmakologie chemická syntéza chemie MeSH
- koncentrace vodíkových iontů MeSH
- lidé MeSH
- molekulární struktura MeSH
- rivastigmin farmakologie chemická syntéza chemie MeSH
- rozpustnost MeSH
- sulfonamidy * farmakologie chemie chemická syntéza MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
PURPOSE: Affinisol HPMC HME is a new popular form of hypromellose specifically designed for the hot melt extrusion and 3D printing of pharmaceutical products. However, reports of its thermal stability include only data obtained under inert N2 atmosphere, which is not consistent with the common pharmaceutical practice. Therefore, detailed investigation of its real-life thermal stability in air is paramount for identification of potential risks and limitations during its high-temperature processing. METHODS: In this work, the Affinisol HPMC HME 15LV powder as well as extruded filaments will be investigated by means of thermogravimetry, differential scanning calorimetry and infrared spectroscopy with respect to its thermal stability. RESULTS: The decomposition in N2 was proceeded in accordance with the literature data and manufacturer's specifications: onset at ~260°C at 0.5°C·min-1, single-step mass loss of 90-95%. However, in laboratory or industrial practice, high-temperature processing is performed in the air, where oxidation-induced degradation drastically changes. The thermogravimetric mass loss in air proceeded in three stages: ~ 5% mass loss with onset at 150°C, ~ 70% mass loss at 200°C, and ~ 15% mass loss at 380°C. Diffusion of O2 into the Affinisol material was identified as the rate-determining step. CONCLUSION: For extrusion temperatures ≥170°C, Affinisol exhibits a significant degree of degradation within the 5 min extruder retention time. Hot melt extrusion of pure Affinisol can be comfortably performed below this temperature. Utilization of plasticizers may be necessary for safe 3D printing.
The present study focused on the more detailed characterization of chitosan-carrageenan-based matrix tablets with respect to their potential utilization for drug targeting in the intestine. The study systematically dealt with the particular stages of the dissolution process, as well as with different views of the physico-chemical processes involved in these stages. The initial swelling of the tablets in the acidic medium based on the combined microscopy-calorimetry point of view, the pH-induced differences in the erosion and swelling of the tested tablets, and the morphological characterization of the tablets are discussed. The dissolution kinetics correlated with the rheological properties and mucoadhesive behavior of the tablets are also reported, and, correspondingly, the formulations with suitable properties were identified. It was confirmed that the formation of the chitosan-carrageenan polyelectrolyte complex may be an elegant and beneficial alternative solution for the drug targeting to the intestine by the matrix tablet.
- Publikační typ
- časopisecké články MeSH
Tablets used for extended drug release commonly contain large amounts of drugs. The corresponding drug release mechanism thus has to be well-known and invariable under numerous conditions in order to prevent any uncontrolled drug release. Particularly important is the stability and invariability of the release mechanism in the presence of alcohol due to the possible occurrence of the dose dumping effect. The effect of 3D printing (3DP) coating on the drug release mechanism and the drug release rate was studied as a possible tool for the prevention of the alcohol-induced dose dumping effect. Three types of matrix tablets (hydrophilic, lipophilic, and hydrophilic-lipophilic) were prepared by the direct compression method and coated using 3DP. The commercial filament of polyvinyl alcohol (PVA) and the filament prepared from hypromellose by hot melt extrusion (HME) were used as coating materials. Both coating materials were characterized by SEM, DSC, Raman spectroscopy, and PXRD during particular stages of the processing/coating procedure. The dissolution behavior of the uncoated and coated tablets was studied in the strongly acidic (pH 1.2) and alcoholic (40% of ethanol) dissolution media. The dissolution tests in the alcoholic medium showed that the Affinisol coating was effective in preventing the dose dumping incidence. The dissolution tests in the acidic dissolution media showed that the Affinisol coating can also be useful for the delayed release of active substances.
- Publikační typ
- časopisecké články MeSH
The objective of the paper is to evaluate the quality of systemic change management (CHM) and readiness for change in five Central European countries. The secondary goal is to identify trends and upcoming changes in the field of digital innovations in healthcare. The results show that all compared countries (regardless of their historical context) deal with similar CHM challenges with a rather similar degree of success. A questionnaire distributed to hospitals clearly showed that there is still considerable room for improvement in terms of the use of specific CHM tools. A review focused on digital innovations based on the PRISMA statement showed that there are five main directions, namely, data collection and integration, telemedicine, artificial intelligence, electronic medical records, and M-Health. In the hospital environment, there are considerable reservations in applying change management principles, as well as the absence of a systemic approach. The main factors that must be monitored for a successful and sustainable CHM include a clearly defined and widely communicated vision, early engagement of all stakeholders, precisely set rules, adaptation to the local context and culture, provision of a technical base, and a step-by-step implementation with strong feedback.
- Publikační typ
- časopisecké články MeSH
This study aims to calculate the costs of prostate cancer radiotherapy in a regional hospital Department of Radiation Oncology equipped with Three-Dimensional Conformal Radiation Therapy (3D-CRT) and Intensity Modulated Radiation Therapy (IMRT) Volumetric Arc Therapy (VMAT) radiation technology, using activity based costing (ABC), and to compare the costs of both methods at the level of component treatment process activities and with respect to insurance reimbursements. The costing was performed based on a sample of 273 IMRT VMAT patients and 312 3D-CRT patients in a regional hospital in the period from 2018 to 2019. The research has highlighted the necessity to place emphasis on factors that may skew the costing results. The resulting output has been supplemented by a sensitivity analysis, whereas the modeled parameter is represented by the time required for one patient fraction on a linear accelerator and the time the Radiology Assistant needs to prepare the complete radiation plan as part of radiotherapy planning. Moreover, the effects of the received grant, in the form of calculated write-offs, are also considered. The case study uses the example of radiotherapy to demonstrate the potential of ABC and suggests considering the application of this method as an effective management tool for cost and economic evaluation as part of comprehensive hospital assessment under the Hospital-Based Health Technology Assessment (HB-HTA) initiative.
- Publikační typ
- časopisecké články MeSH
Non-isothermal differential scanning calorimetry was used to study the influences of particle size and mechanically induced defects on the recrystallization kinetics of amorphous Enzalutamide. Enzalutamide prepared by hot melt extrusion and spray-drying was used as a model material. The recrystallization rate was primarily accelerated by the presence of the processing-damaged surface of the powder particles. The actual surface/volume ratio associated with decreasing particle size fulfilled only a secondary role. Interestingly, higher quench rate during the extrusion led to a formation of thermally less stable material (with the worse stability being manifested via lower activation energy of crystal growth in the amorphous matrix). This can be the consequence of the formation of looser structure more prone to rearrangements. The recrystallization kinetics of the prepared Enzalutamide amorphous materials was described by the two-parameter autocatalytic kinetic model. The modified single-curve multivariate kinetic analysis (optimized for the data obtained at heating rate 0.5 °C•min-1) was used to calculate the extrapolated kinetic predictions of long-term isothermal crystal growth. The predictions were made for the temperatures from the range of drug shelf-life and processing for each particle size fraction. By the combination of the mass-weighted predictions for the individual powder fractions it was possible to obtain a very reasonable (temperature-extrapolated) prediction of the crystallization rate for the as-prepared unsieved powdered amorphous Enzalutamide.
Článek představuje kazuistiku vzácné příčiny hluchoty. Pacientka s obrazem akutní pansinusitidy s mastoiditidou hospitalizována k i.v. ATB terapii a chirurgickému řešení. Z objektivních vyšetření výrazná hlenovitá až hlenohnisavá sekrece z nosu, hlenovitá sekrece ve středouší oboustranně a počínající protruze bulbu vpravo. Na CT a MRI kompletní zastření všech VDN a mastoidů. Subjektivním steskům dominovalo především výrazné zhoršení sluchu, na pravém uchu prakticky až k hluchotě. Po provedené FESS bez regrese patologického stavu. Výsledky histologického vyšetření vzorků polypózní tkáně odebrané při operaci odhalily přítomnost tumoru. Série klinických vyšetření prokázala přítomnost pokročilého karcinomu prsu se vzdálenými metastázami (stadium IV). Prvními příznaky tohoto onemocnění byla akutní pansinusitida s mastoiditidou, oční příznaky s protruzí bulbu a výrazné zhoršení sluchu.
The article presents an uncommon case of deafness. A patient with symptoms of acute rhinosinusitis with mastoiditis was hospitalized for antibiotics therapy and surgery. Objective examinations were characterized by muco-purulent nasal discharge, mucous middle ear secretion of both sides and starting protrusion of right eyeball. CT and MRI images were with complete obstruction of all nasal cavities and mastoids. The patient suffered from significant deterioration of hearing, up to deafness on the right side. After the FESS, there was no regression of the pathological condition. The results of histological examination of polypous tissue revealed the presence of advanced breast cancer with distant metastasis (stage IV). The first signs of this disease were acute pansinusitis with mastoiditis, eyeball protrusion and significant deterioration of hearing.
- MeSH
- endoskopie metody MeSH
- hluchota * etiologie MeSH
- lidé MeSH
- mastoiditida etiologie patologie MeSH
- nádory prsu * komplikace MeSH
- paranazální dutiny patologie MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- práce podpořená grantem MeSH
