In vitro dissolution testing is commonly performed to ensure that oral solid dosage medicines are of high quality and will achieve their targeted in vivo performance. However, this testing is time and material consuming. Therefore, pharmaceutical companies have been developing predictive dissolution models (PDMs) for drug product release based on fast at- and/or on-line measurements, including real-time release testing of dissolution (RTRT-D). Recently, PDMs have seen acceptance by major regulatory bodies as release tests for the dissolution critical quality attribute. In this paper, several methodologies are described to develop and validate a fit-for-purpose model, then to implement it as a surrogate release test for dissolution. These approaches are further exemplified by real-life case studies, which demonstrate that PDMs for release are not only viable but more sustainable than in vitro dissolution testing and can significantly accelerate drug product release. The rise of continuous manufacturing within the pharmaceutical industry further favors the implementation of real-time release testing. Therefore, a steep uptake of PDMs for release is expected once this methodology is globally accepted. To that end, it is advantageous for global regulators and pharmaceutical innovators to coalesce around a harmonized set of expectations for development, validation, implementation, and lifecycle of PDMs as part of drug product release testing.

• MeSH
• aplikace orální MeSH
• farmaceutická chemie metody   MeSH
• léčivé přípravky chemie   aplikace a dávkování   MeSH
• lidé MeSH
• příprava léků MeSH
• rozpustnost MeSH
• schvalování léčiv MeSH
• uvolňování léčiv * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Sborník sloupků publikovaných v novinách Seznam Zprávy, které se zaměřují na aktuální politické a společenské dění, zejména v Česku, a představují názory autora. Určeno široké veřejnosti.; Už vás někdy napadlo, proč se ve společnosti opakují stále stejné chyby? Proč ti, kteří zpívali hymny o svobodě, dnes sedí v pohodlí funkcí a moci? Tato kniha vám nabízí odpovědi – a zároveň vás donutí přemýšlet nad vaší vlastní rolí v tomto příběhu. Kritické diagnózy nejsou čtením pro slabé povahy. Přinutí vás vidět svět jinak, opustit komfortní zónu a podívat se pravdě do očí. Ať už jste student, profesionál, rodič nebo politik, kniha inspiruje k otázce: Co mohu já udělat, aby byla naše společnost lepší? Autor přesvědčivě ukazuje, kde jsme jako národ uspěli, a kde selhali. Sloupky jsou břitké, přesné a často nepohodlné – pro každého. Právě proto jsou tak důležité. Odhalují to, co se skrývá pod povrchem každodenního dění. Čtenář může nahlédnout do zákulisí mocenských her, osobních selhání, ale také do nadějí a možností, kam bychom mohli směřovat. Josef Veselka není politik ani novinář s agendou. Je lékař, který roky vedl prestižní kardiologickou kliniku, a zároveň člověk, jenž se čtenářům rozhodl nabídnout svůj pohled na českou společnost. Tato dvojí zkušenost – odborná i lidská – činí jeho texty mimořádně autentickými a důvěryhodnými. Autorův pronikavý pohled do nedávné historie – od revolučních nadějí po současné rozčarování – je varováním i lekcí. Ukazuje, jak snadno může být ztracena svoboda, jak hluboko může zakořenit pokrytectví a jak důležitá je morálka. Každý sloupek je doplněn stručným vysvětlením kontextu, ve kterém vznikal. Kniha tedy není jen aktuální výpovědí, ale i záznamem pro budoucí generace. Je jako víno – čím déle zraje, tím více chutí a vrstev objevíte. Kritické diagnózy: 100 sloupků, které rozkrývají společenské paradoxy dnešního Česka.

• MeSH
• dějiny 21. století MeSH
• politika MeSH
• poskytování zdravotní péče MeSH
• postoj MeSH
• sociologické faktory MeSH
• Check Tag
• dějiny 21. století MeSH
• Publikační typ
• novinové články MeSH
• populární práce MeSH
• sborníky MeSH
• Geografické názvy
• Česká republika MeSH

• Konspekt
• Vnitropolitický vývoj, politický život
• NLK Obory
• politologie, politika, zdravotní politika
• sociologie

• O autorovi
• Seznam.cz (firma) Autorita

Spinal cord injury (SCI) results in paralysis, driven partly by widespread glutamate-induced secondary excitotoxic neuronal cell death in and around the injury site. While there is no curative treatment, the standard of care often requires interventive decompression surgery and repair of the damaged dura mater close to the injury locus using dural substitutes. Such intervention provides an opportunity for early and local delivery of therapeutics directly to the injured cord via a drug-loaded synthetic dural substitute for localized pharmacological therapy. Riluzole, a glutamate-release inhibitor, has shown neuroprotective potential in patients with traumatic SCI, and therefore, this study aimed to develop an electrospun riluzole-loaded synthetic dural substitute patch suitable for the treatment of glutamate-induced injury in neurons. A glutamate-induced excitotoxicity was optimized in SH-SY5Y cells by exploring the effect of glutamate concentration and exposure duration. The most effective timing for administering riluzole was found to be at the onset of glutamate release as this helped to limit extended periods of glutamate-induced excitotoxic cell death. Riluzole-loaded patches were prepared by using blend electrospinning. Physicochemical characterization of the patches showed the successful encapsulation of riluzole within polycaprolactone fibers. A drug release study showed an initial burst release of riluzole within the first 24 h, followed by a sustained release of the drug over 52 days to up to approximately 400 μg released for the highest loading of riluzole within fiber patches. Finally, riluzole eluted from electrospun fibers remained pharmacologically active and was capable of counteracting glutamate-induced excitotoxicity in SH-SY5Y cells, suggesting the clinical potential of riluzole-loaded dural substitutes in counteracting the effects of secondary injury in the injured spinal cord.

• MeSH
• implantované léky MeSH
• kyselina glutamová metabolismus   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• neurony účinky léků   MeSH
• neuroprotektivní látky * aplikace a dávkování   chemie   farmakologie   MeSH
• polyestery chemie   MeSH
• poranění míchy * farmakoterapie   MeSH
• riluzol * aplikace a dávkování   chemie   farmakologie   MeSH
• uvolňování léčiv MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

The semi-synthetic cannabinoid hexahydrocannabinol (HHC) has become a highly discussed topic in forensic toxicology since 2022 due to its legal availability at this time and its psychoactive effects. This study aimed to investigate the pharmacokinetics, effects, and immunological detectability of HHC after oral (25 mg HHC fruit gum) and inhalative (three puffs from HHC vape) consumption with three participants per group. Serum (up to 48 h), urine (up to five days), and saliva (up to 48 h) samples were collected at different relevant time points and analyzed by HPLC-MS/MS for (9R)/(9S)-HHC, 11-hydroxy-HHC, and (9R)/(9S)-HHC carboxylic acid with a fully validated method. Additionally, immunological detectability was investigated with three different commercially available tests. To address the psychoactive effects, the subjective "high" feeling (scale 0-10) was monitored and different psychophysical tests (e.g. modified Romberg test, walk and turn) were conducted. Overall, the pharmacokinetics and effects of HHC were comparable to tetrahydrocannabinol (THC). However, the route of administration as well as inter-individual factors played a crucial role regarding maximum concentrations, pharmacokinetic profiles, and psychoactive effects.

• MeSH
• agonisté kanabinoidních receptorů farmakokinetika   farmakologie   MeSH
• aplikace inhalační * MeSH
• aplikace orální * MeSH
• dospělí MeSH
• emoce účinky léků   MeSH
• farmakokinetika * MeSH
• imunologické testy MeSH
• kanabinoidy * analýza   krev   farmakokinetika   farmakologie   moč   MeSH
• kapalinová chromatografie-hmotnostní spektrometrie MeSH
• lidé MeSH
• psychofyziologie * MeSH
• psychotropní léky * analýza   krev   farmakokinetika   farmakologie   moč   MeSH
• sliny chemie   MeSH
• tetrahydrokanabinol farmakokinetika   farmakologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

With an increasing focus on sustainable technologies in the pharmaceutical industry, milling provides a solvent-free approach to improve drug dissolution. Milling of drugs with an excipient offers additional opportunities to achieve supersaturation kinetics. Therefore, this work aims to present insights of co-milling fenofibrate and apremilast, two good glass formers with low and high glass transition temperatures (Tgs) respectively. Drugs were co-milled with croscarmellose sodium for various process durations followed by thermal analysis, investigation of crystallinity, surface area and dissolution. The dissolution enhancement of the low-Tg glass former fenofibrate highly correlated with the process-induced increase in surface area of co-milled systems (R2 = 0.96). In contrast, the high-Tg glass former apremilast lost its crystalline order gradually after ≥ 10 min of co-milling, and favourable supersaturation kinetics during biorelevant dissolution testing were observed. Interestingly, the melting point of co-milled apremilast decreased and linearly correlated with the highest measured drug concentration (cmax) during in vitro dissolution (onset temperature R2 = 0.98; peak temperature R2 = 0.96). The melting point depression remained stable after 90 days for apremilast, whereas fenofibrate co-milled for 20 min or more showed an increase in melting point upon storage. This study demonstrated that co-milling with croscarmellose sodium is ideally suited to good glass formers with a high Tg. The melting point depression is thereby proposed as an easily accessible critical quality attribute to estimate likely dissolution performance of drugs in dry co-milled formulations.

• MeSH
• Aspirin chemie   analogy a deriváty   MeSH
• fenofibrát * chemie   MeSH
• pomocné látky chemie   MeSH
• příprava léků metody   MeSH
• rozpustnost MeSH
• sklo * chemie   MeSH
• thalidomid analogy a deriváty   MeSH
• tranzitní teplota MeSH
• uvolňování léčiv MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH

The utilization of 3D printing- digital light processing (DLP) technique, for the direct fabrication of microneedles encounters the problem of drug solubility in printing resin, especially if it is predominantly composed of water. The possible solution how to ensure ideal belonging of drug and water-based printing resin is its pre-formulation in nanosuspension such as nanocrystals. This study investigates the feasibility of this approach on a resin containing nanocrystals of imiquimod (IMQ), an active used in (pre)cancerous skin conditions, well known for its problematic solubility and bioavailability. The resin blend of polyethylene glycol diacrylate and N-vinylpyrrolidone, and lithium phenyl-2,4,6-trimethylbenzoylphosphinate as a photoinitiator, was used, mixed with IMQ nanocrystals in water. The final microneedle-patches had 36 cylindrical microneedles arranged in a square grid, measuring approximately 600 μm in height and 500 μm in diameter. They contained 5wt% IMQ, which is equivalent to a commercially available cream. The homogeneity of IMQ distribution in the matrix was higher for nanocrystals compared to usual crystalline form. The release of IMQ from the patches was determined ex vivo in natural skin and revealed a 48% increase in efficacy for nanocrystal formulations compared to the crystalline form of IMQ.

• MeSH
• 3D tisk * MeSH
• aplikace kožní MeSH
• imichimod * chemie   aplikace a dávkování   MeSH
• jehly * MeSH
• kožní absorpce MeSH
• kůže metabolismus   MeSH
• lékové transportní systémy přístrojové vybavení   MeSH
• mikroinjekce přístrojové vybavení   MeSH
• nanočástice * chemie   aplikace a dávkování   MeSH
• polyethylenglykoly chemie   aplikace a dávkování   MeSH
• povidon chemie   MeSH
• rozpustnost * MeSH
• uvolňování léčiv MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Detrimental effects of misinformation were observed during the COVID-19 pandemic. Presently, amid Russia's military aggression in Ukraine, another wave of misinformation is spreading on the web and impacting our daily lives, with many citizens and politicians embracing Russian propaganda narratives. Despite the lack of an objective connection between these 2 societal issues, anecdotal observations suggest that supporters of misinformation regarding COVID-19 (BM-C) have also adopted misinformation about the war in Ukraine (BM-U) while sharing similar media use patterns and political attitudes. OBJECTIVE: The aim of this study was to determine whether there is a link between respondents' endorsement of the 2 sets of misinformation narratives, and whether some of the selected factors (media use, political trust, vaccine hesitancy, and belief rigidity) are associated with both BM-C and BM-U. METHODS: We conducted a survey on a nationally representative sample of 1623 individuals in the Czech Republic. Spearman correlation analysis was performed to identify the relationship between BM-C and BM-U. In addition, multiple linear regression was used to determine associations between the examined factors and both sets of misinformation. RESULTS: We discovered that BM-C and BM-U were moderately correlated (Spearman ρ=0.57; P<.001). Furthermore, increased trust in Russia and decreased trust in the local government, public media, and Western allies of the Czech Republic predicted both BM-C and BM-U. Media use indicating frustration with and avoidance of public or mainstream media, consumption of alternative information sources, and participation in web-based discussions indicative of epistemic bubbles predicted beliefs in misinformation narratives. COVID-19 vaccine refusal predicted only BM-C but not BM-U. However, vaccine refusers were overrepresented in the BM-U supporters (64/161, 39.8%) and undecided (128/505, 25.3%) individuals. Both beliefs were associated with belief rigidity. CONCLUSIONS: Our study provides empirical evidence that supporters of COVID-19 misinformation were susceptible to ideological misinformation aligning with Russian propaganda. Supporters of both sets of misinformation narratives were primarily linked by their shared trust or distrust in the same geopolitical actors and their distrust in the local government.

• MeSH
• COVID-19 * prevence a kontrola   epidemiologie   psychologie   MeSH
• dospělí MeSH
• důvěra MeSH
• komunikace * MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• odkládání očkování psychologie   MeSH
• pandemie MeSH
• politika MeSH
• průzkumy a dotazníky MeSH
• SARS-CoV-2 MeSH
• senioři MeSH
• vakcíny proti COVID-19 aplikace a dávkování   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Rusko MeSH
• Ukrajina MeSH

Spray drying and hot-melt extrusion are among the most prevalent preparation techniques used in the pharmaceutical industry to produce amorphous solid dispersions (ASDs). This study advances previous research by integrating sample production, comprehensive analytical characterization, intrinsic dissolution rate measurements, and assessments of the behavior of ASDs under elevated temperature and humidity conditions. The study focuses on indomethacin, a widely used model for poorly soluble drugs, processed with PVP K30 or HPMC E5, both commonly used polymers. The findings demonstrate that hot-melt extruded samples exhibit superior stability against recrystallization, whereas spray dried samples achieve higher intrinsic dissolution rates. Furthermore, PVP K30 significantly outperforms HPMC E5 in the co-processing of indomethacin, enhancing both the intrinsic dissolution rate and the stability.

• MeSH
• deriváty hypromelózy chemie   MeSH
• farmaceutická chemie metody   MeSH
• indomethacin * chemie   MeSH
• krystalizace * MeSH
• povidon chemie   MeSH
• příprava léků metody   MeSH
• rozpustnost * MeSH
• sprejové sušení * MeSH
• stabilita léku * MeSH
• technologie extruze tavenin * metody   MeSH
• uvolňování léčiv MeSH
• vlhkost MeSH
• vysoká teplota MeSH
• vysoušení metody   MeSH
• Publikační typ
• časopisecké články MeSH

In recent years, deep eutectic solvents (DESs) with their outstanding solubilization properties have emerged as strong candidates for oral enabling formulations of poorly soluble drugs. This study explores the use of drug-based therapeutic DESs (THEDESs) to solubilize a poorly soluble compound with the aim of providing a fixed-dose combination of two complementary therapeutic agents. Specifically, potential anticancer effects of ibuprofen (IBU) are harnessed in a novel type of THEDES to dissolve higher amounts of abiraterone acetate (AbAc), an antitumor agent. Four IBU-based combinations were studied: 1:4 M ratio with octanoic acid (OctA), 1:5 with nonanoic acid (NonA), 1:3 with decanoic acid (DeA) or 1:2 with dodecanoic acid (DoA). Fatty acids of different chain lengths were analyzed and discussed considering surface charge densities obtained via quantum chemistry. The THEDESs listed could apparently dissolve AbAc amounts up to 1311.0 ± 125.4 mg/g in IBU:OctA THEDES, 1151.7 ± 22.2 mg/g in IBU:NonA, 1160.4 ± 33.5 mg/g in IBU:DeA, and 231.3 ± 10.7 mg/g in IBU:DoA. In vitro dissolution of the simultaneously released drugs reached 37.8 ± 9.0 % to 64.2 ± 1.0 % for IBU and 5.0 ± 3.3 % to 19.4 ± 0.1 % for AbAc. This increased to between 60.4 ± 2.8 % and 79.4 ± 5.0 % of released IBU, and 23.6 ± 1.0 % to 57.3 ± 5.8 % of released AbAc, with 20 % (w/w) Tween 80 added to the formulations. This showed the significant potential of drug-containing THEDESs as solubilizing agents for poorly soluble drugs, in the form of fixed-dose combinations of synergistic APIs.

• MeSH
• abirateron * chemie   aplikace a dávkování   MeSH
• farmaceutická chemie metody   MeSH
• fixní kombinace léků MeSH
• ibuprofen * chemie   aplikace a dávkování   MeSH
• mastné kyseliny chemie   MeSH
• příprava léků metody   MeSH
• protinádorové látky chemie   aplikace a dávkování   MeSH
• rozpouštědla * chemie   MeSH
• rozpustnost * MeSH
• uvolňování léčiv MeSH
• Publikační typ
• časopisecké články MeSH

Free radical polymerization technique was used to formulate Poloxamer-188 based hydrogels for controlled delivery. A total of seven formulations were formulated with varying concentrations of polymer, monomer ad cross linker. In order to assess the structural properties of the formulated hydrogels, Fourier Transform Infrared Spectroscopy (FTIR), Thermogravimetric analysis (TGA), Differential Scanning Calorimetry (DSC), Scanning electron microscopy (SEM), and X-ray diffraction (XRD) were carried out. To assess the effect of pH on the release of the drug from the polymeric system, drug release studies were carried in pH 1.2 and 7.4 and it was found that release of the drug was significant in pH 7.4 as compared to that of pH 1.2 which confirmed the pH responsiveness of the system. Different kinetic models were also applied to the drug release to evaluate the mechanism of the drug release from the system. To determine the safety and biocompatibility of the system, toxicity study was also carried out for which healthy rabbits were selected and formulated hydrogels were orally administered to the rabbits. The results obtained suggested that the formulated poloxamer-188 hydrogels are biocompatible with biological system and have the potential to serve as controlled drug delivery vehicles.

• MeSH
• akrylové pryskyřice * chemie   MeSH
• diferenciální skenovací kalorimetrie MeSH
• difrakce rentgenového záření MeSH
• hydrogely * chemie   MeSH
• koncentrace vodíkových iontů MeSH
• králíci MeSH
• lékové transportní systémy MeSH
• léky s prodlouženým účinkem chemie   farmakokinetika   MeSH
• mikroskopie elektronová rastrovací MeSH
• nosiče léků chemie   MeSH
• poloxamer * chemie   MeSH
• spektroskopie infračervená s Fourierovou transformací MeSH
• termogravimetrie MeSH
• timolol * aplikace a dávkování   farmakokinetika   chemie   MeSH
• uvolňování léčiv MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH