- MeSH
- digoxin chemická syntéza farmakologie MeSH
- lidé MeSH
- odměny a ceny MeSH
- příprava léků * MeSH
- studenti farmacie MeSH
- Check Tag
- lidé MeSH
V článku je zpracována problematika empirické perorální antibiotické terapie nejčastějších akutních komunitních bakteriální infekcí u dětí, a sice tonzilitidy, otitis media, sinusitidy, pneumonie, cystitidy, pyelonefritidy, erysipelu, flegmóny, impetiga a erythema migrans. Kromě antibiotik první volby jsou uvedeny i alternativy při výpadku antibiotik nebo při alergii. Součástí doporučení jsou také magistraliter receptury vybraných antibiotik. V článku je dále věnována pozornost klasifikaci antibiotik AWaRe, která rozděluje dostupná antibiotika do tří skupin podle rizika indukce rezistence bakterií.
This article addresses the issue of empirical oral antibiotic therapy for the most common acute community-acquired bacterial infections in children, specifically tonsillitis, otitis media, sinusitis, pneumonia, cystitis, pyelonephritis, erysipelas, cellulitis, impetigo, and erythema migrans. In addition to first-choice antibiotics, alternatives are provided in cases of antibiotic shortages or allergies. The recommendations also include magistral (compounded, pharmacist-prepared) formulas for selected antibiotics. The article further focuses on the AWaRe classification of antibiotics, which divides available antibiotics into three groups according to the risk of inducing bacterial resistance.
- MeSH
- antibakteriální látky * farmakologie klasifikace terapeutické užití MeSH
- antibiotická rezistence MeSH
- bakteriální infekce * epidemiologie farmakoterapie klasifikace MeSH
- bakteriální pneumonie farmakoterapie MeSH
- dítě MeSH
- impetigo etiologie farmakoterapie klasifikace MeSH
- lidé MeSH
- otitis media farmakoterapie klasifikace MeSH
- příprava léků klasifikace metody MeSH
- sinusitida farmakoterapie MeSH
- směrnice pro lékařskou praxi jako téma MeSH
- tonzilitida farmakoterapie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- přehledy MeSH
Sildenafil citrate has low oral bioavailability, systemic adverse effects, and a relatively delayed action. These issues may be addressed through direct transdermal delivery to the penis. This study aims to investigate the microemulsion formulation of the drug for effective transdermal delivery. Sildenafil citrate was formulated as a microemulsion using clove oil, dimethyl sulphoxide, phosphate buffer (pH 7), propylene glycol, Tween®80, and distilled water. Different proportions of these components were used to create six formulations of the microemulsion (F1-F6), which were then characterised by their physical appearance and clarity, pH, viscosity, conductivity, percent transmission, and droplet size. Furthermore, the stability, content analysis, in-vitro drug release, and transdermal permeation of sildenafil citrate from the generated drug-loaded microemulsions were studied. All prepared formulas contained nano-sized oil droplets (less than 20 nm), and the pH values were within the range of skin pH; however, two formulas were not transparent. Additionally, all formulations were thermodynamically stable, passing freeze-thaw, heating-cooling, and centrifugation tests. Next, the formulas demonstrated zero-order release kinetics, indicating that they can provide a sustained release profile for sildenafil citrate. Finally, the microemulsion formulation exhibited a 2.8-fold enhancement in skin permeation compared with that of the sildenafil citrate suspension. The prepared microemulsions demonstrated beneficial physical properties and skin permeation profiles that are promising for the local administration of sildenafil citrate.
- Klíčová slova
- mikroemulze,
- MeSH
- aplikace kožní * MeSH
- emulze MeSH
- hřebíčkový olej MeSH
- krysa rodu rattus MeSH
- lékové formy MeSH
- modely u zvířat MeSH
- permeabilita MeSH
- příprava léků metody MeSH
- sildenafil citrát * aplikace a dávkování farmakokinetika farmakologie MeSH
- stabilita léku MeSH
- suspenze MeSH
- uvolňování léčiv MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- klinická studie MeSH
The bioavailability of rivaroxaban at the higher doses (15 and 20 mg) is considerably reduced when the drug is administered on an empty stomach. This can lead to inadequate anticoagulant effect, and therefore, it is recommended to use the higher doses at fed state. However, proper posology may represent a barrier for some patients. Therefore, the aim of this study was to evaluate innovative rivaroxaban-containing formulations designed to eliminate the food effect to ensure reliable absorption and thus to improve patient adherence with the treatment. Three prototypes (Cocrystal, HPMCP and Kollidon) with rivaroxaban were developed and their bioavailability and food effect in comparison to the reference product was tested in open label, randomized, single oral dose, crossover studies, where test products were administered under fasting and fed conditions and the reference product was administered under fed conditions. Comparable bioavailability for all tested prototypes both under fed and fasting conditions was demonstrated as the 90% confidence intervals of the geometric mean ratios for area under the concentration-time curve remained within the standard acceptance range of 80.00%-125.00%. An innovative immediate release form of rivaroxaban with no food effect on drug bioavailability has been developed, which may represent an important step toward increasing adherence, improving treatment outcome and reducing health care costs.
- MeSH
- aplikace orální MeSH
- biologická dostupnost * MeSH
- dospělí MeSH
- inhibitory faktoru Xa farmakokinetika aplikace a dávkování MeSH
- interakce mezi potravou a léky * MeSH
- jídla MeSH
- klinické křížové studie * MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- omezení příjmu potravy * MeSH
- příprava léků metody MeSH
- rivaroxaban * farmakokinetika aplikace a dávkování MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
There is increasing pharmaceutical interest in deep eutectic solvents not only as a green alternative to organic solvents in drug manufacturing, but also as liquid formulation for drug delivery. The present work introduces a hydrophobic deep eutectic solvent (HDES) to the field of lipid-based formulations (LBF). Phase behavior of a mixture with 2:1 M ratio of decanoic- to dodecanoic acid was studied experimentally and described by thermodynamic modelling. Venetoclax was selected as a hydrophobic model drug and studied by atomistic molecular dynamics simulations of the mixtures. As a result, valuable molecular insights were gained into the interaction networks between the different components. Moreover, experimentally the HDES showed greatly enhanced drug solubilization compared to conventional glyceride-based vehicles, but aqueous dispersion behavior was limited. Hence surfactants were studied for their ability to improve aqueous dispersion and addition of Tween 80 resulted in lowest droplet sizes and high in vitro drug release. In conclusion, the combination of HDES with surfactant(s) provides a novel LBF with high pharmaceutical potential. However, the components must be finely balanced to keep the integrity of the solubilizing HDES, while enabling sufficient dispersion and drug release.
- MeSH
- chemie farmaceutická metody MeSH
- hydrofobní a hydrofilní interakce * MeSH
- kyseliny laurové chemie MeSH
- lipidy * chemie MeSH
- oleje chemie MeSH
- polysorbáty chemie MeSH
- povrchově aktivní látky * chemie MeSH
- příprava léků * metody MeSH
- rozpouštědla * chemie MeSH
- rozpustnost * MeSH
- simulace molekulární dynamiky * MeSH
- sulfonamidy chemie aplikace a dávkování MeSH
- uvolňování léčiv * MeSH
- Publikační typ
- časopisecké články MeSH
Inhalation drug administration is increasingly used for local pharmacotherapy of lung disorders and as an alternative route for systemic drug delivery. Modern inhalation powder systems aim to target drug deposition in the required site of action. Large porous particles (LPP), characterized by an aerodynamic diameter over 5 μm, density below 0.4 g/cm3, and the ability to avoid protective lung mechanisms, come to the forefront of the research. They are mostly prepared by spray techniques such as spray drying or lyophilization using pore-forming substances (porogens). These substances could be gaseous, solid, or liquid, and their selection depends on their polarity, solubility, and mutual compatibility with the carrier material and the drug. According to the pores-forming mechanism, porogens can be divided into groups, such as osmogens, extractable porogens, and porogens developing gases during decomposition. This review characterizes modern trends in the formulation of solid microparticles for lung delivery; describes the mechanisms of action of the most often used porogens, discusses their applicability in various formulation methods, emphasizes spray techniques; and documents discussed topics by examples from experimental studies.
- MeSH
- aplikace inhalační MeSH
- chemie farmaceutická metody MeSH
- lidé MeSH
- plíce * metabolismus účinky léků MeSH
- poréznost MeSH
- prášky, zásypy, pudry MeSH
- příprava léků metody MeSH
- systémy cílené aplikace léků * metody MeSH
- velikost částic * MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Co-milling is an effective technique for improving dissolution rate limited absorption characteristics of poorly water-soluble drugs. However, there is a scarcity of models available to forecast the magnitude of dissolution rate improvement caused by co-milling. Therefore, this study endeavoured to quantitatively predict the increase in dissolution by co-milling based on drug properties. Using a biorelevant dissolution setup, a series of 29 structurally diverse and crystalline drugs were screened in co-milled and physically blended mixtures with Polyvinylpyrrolidone K25. Co-Milling Dissolution Ratios after 15 min (COMDR15 min) and 60 min (COMDR60 min) drug release were predicted by variable selection in the framework of a partial least squares (PLS) regression. The model forecasts the COMDR15 min (R2 = 0.82 and Q2 = 0.77) and COMDR60 min (R2 = 0.87 and Q2 = 0.84) with small differences in root mean square errors of training and test sets by selecting four drug properties. Based on three of these selected variables, applicable multiple linear regression equations were developed with a high predictive power of R2 = 0.83 (COMDR15 min) and R2 = 0.84 (COMDR60 min). The most influential predictor variable was the median drug particle size before milling, followed by the calculated drug logD6.5 value, the calculated molecular descriptor Kappa 3 and the apparent solubility of drugs after 24 h dissolution. The study demonstrates the feasibility of forecasting the dissolution rate improvements of poorly water-solube drugs through co-milling. These models can be applied as computational tools to guide formulation in early stage development.
Transferring an existing marketed pharmaceutical product from batch to continuous manufacturing (CM) without changes in regulatory registration is a challenging task in the pharmaceutical industry. Continuous manufacturing can provide an increased production rate and better equipment utilisation while retaining key quality attributes of the final product. Continuous manufacturing necessitates the monitoring of critical quality attributes in real time by appropriate process analytical tools such as near infra-red (NIR) probes. The present work reports a successful transfer of an existing drug product from batch to continuous manufacturing process without changing the formulation. A key step was continuous powder blending, whose design and operating parameters including weir type, agitation rate, dynamic hold-up and residence time were systematically investigated with respect to process repeatability. A NIR-based multivariate data model for in-line composition monitoring has been developed and validated against an existing quality control method for measuring tablet content uniformity. A continuous manufacturing long-run with a throughput of 30 kg/h (approx. 128,000 tablets per hour), uninterrupted for 320 min, has been performed to test and validate the multivariate data model as well as the batch to continuous process transfer. The final disintegration and dissolution properties of tablets manufactured by the continuous process were found to be equivalent to those manufactured by the original batch process.
- MeSH
- blízká infračervená spektroskopie metody MeSH
- chemie farmaceutická metody MeSH
- farmaceutická technologie * metody MeSH
- pomocné látky chemie MeSH
- prášky, zásypy, pudry chemie MeSH
- příprava léků metody MeSH
- řízení kvality MeSH
- rozpustnost MeSH
- tablety * MeSH
- uvolňování léčiv MeSH
- Publikační typ
- časopisecké články MeSH
The transfer from batch-based to continuous tablet manufacturing increases the quality and efficiency of processes. Nonetheless, as in the development of a batch process, the continuous process design requires optimization studies to ensure a robust process. In this study, processing of a commercially batch-manufactured tablet product was tested with two continuous direct compression lines while keeping the original formulation composition and tablet quality requirements. Tableting runs were conducted with different values of process parameters. Changes in parameter settings were found to cause differences in tablet properties. Most of these quality properties could be controlled and maintained within the set limits effortlessly already at this stage of studies. However, the API content and content uniformity seemed to require more investigation. The observed content uniformity challenges were traced to individual tablets with a high amount of API. This was suspected to be caused by API micro-agglomerates since tablet weight variability did not explain the issue. This could be solved by adding a mill between two blenders in the process line. Overall, this case study produced promising results with both tested manufacturing lines since many tablet properties complied with the test result limits without optimization of process parameter settings.
Článek se zabývá možnostmi perorální suplementace třech vybraných iontů - sodných, draselných a fosfátových, pomocí individuálně připravovaných léčivých přípravků. Tvoří přehled nejčastěji používaných magistraliter receptur ve Fakultní nemocnici v Motole. Zabývá se popisem dostupných surovin a teoretickou charakteristikou iontů. U vybraných receptur je uvedeno množství iontů jak v hmotnostním, tak i v molárním vyjádření. Receptury reflektují potřebu suplementace iontů ve vhodných dávkách a vhodné lékové formě podle individuálních potřeb pacientů.
The article deals with the possibilities of oral supplementation of three selected ions - sodium, potassium and phosphate, by means of individually prepared medicines. It forms an overview of the most frequently used extemporaneous prescriptions in the University Hospital in Motol. It deals with the description of available raw materials and theoretical characteristics of ions. For selected formulations, the amount of ions is given in both mass and molar terms. The formulas reflect the need for ion supplementation in appropriate doses and appropriate dosage form according to the individual needs of patients.
