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The development of novel dry powders for dry powder inhalers (DPIs) requires the in vitro assessment of DPI aerodynamic performance. As a potential complementary method, in silico numerical simulations can provide additional information about the mechanisms that guide the particles and their behavior inside DPIs. The aim of this study was to apply computational fluid dynamics (CFDs) coupled with a discrete phase model (DPM) to describe the forces and particle trajectories inside the RS01 ® as a model DPI device. The methodology included standard fluid flow equations but also additional equations for the particle sticking mechanism, as well as particle behavior after contacting the DPI wall surface, including the particle detachment process. The results show that the coefficient of restitution between the particle and the impact surface does not have a high impact on the results, meaning that all tested combinations gave similar output efficiencies and particle behaviors. No sliding or rolling mechanisms were observed for the particle detachment process, meaning that simple bouncing off or deposition particle behavior is present inside DPIs. The developed methodology can serve as a basis for the additional understanding of the particles' behavior inside DPIs, which is not possible using only in vitro experiments; this implies the possibility of increasing the efficiency of DPIs.

In vitro assessment of dry powders for inhalation (DPIs) aerodynamic performance is an inevitable test in DPI development. However, contemporary trends in drug development also implicate the use of in silico methods, e.g., computational fluid dynamics (CFD) coupled with discrete phase modeling (DPM). The aim of this study was to compare the designed CFD-DPM outcomes with the results of three in vitro methods for aerodynamic assessment of solid lipid microparticle DPIs. The model was able to simulate particle-to-wall sticking and estimate fractions of particles that stick or bounce off the inhaler's wall; however, we observed notable differences between the in silico and in vitro results. The predicted emitted fractions (EFs) were comparable to the in vitro determined EFs, whereas the predicted fine particle fractions (FPFs) were generally lower than the corresponding in vitro values. In addition, CFD-DPM predicted higher mass median aerodynamic diameter (MMAD) in comparison to the in vitro values. The outcomes of different in vitro methods also diverged, implying that these methods are not interchangeable. Overall, our results support the utility of CFD-DPM in the DPI development, but highlight the need for additional improvements in these models to capture all the key processes influencing aerodynamic performance of specific DPIs.

This study aims to understand the absorption patterns of three different kinds of inhaled formulations via in silico modeling using budesonide (BUD) as a model drug. The formulations investigated in this study are: (i) commercially available micronized BUD mixed with lactose (BUD-PT), (ii) BUD nanocrystal suspension (BUD-NC), (iii) BUD nanocrystals embedded hyaluronic acid microparticles (BUD-NEM). The deposition patterns of the three inhaled formulations in the rats' lungs were determined in vivo and in silico predicted, which were used as inputs in GastroPlus™ software to predict drug absorption following aerosolization of the tested formulations. BUD pharmacokinetics, estimated based on intravenous data in rats, was used to establish a drug-specific in silico absorption model. The BUD-specific in silico model revealed that drug pulmonary solubility and absorption rate constant were the key factors affecting pulmonary absorption of BUD-NC and BUD-NEM, respectively. In the case of BUD-PT, the in silico model revealed significant gastrointestinal absorption of BUD, which could be overlooked by traditional in vivo experimental observation. This study demonstrated that in vitro-in vivo-in silico approach was able to identify the key factors that influence the absorption of different inhaled formulations, which may facilitate the development of orally inhaled formulations with different drug release/absorption rates., Competing Interests: The authors declare that there is no conflict of interest., (© 2021 Shenyang Pharmaceutical University. Published by Elsevier B.V.)

The aim of this study was to optimize the parameters of the complex melt-emulsification process coupled with the spray-drying, in order to maintain the balance between solid lipid microparticles (SLMs) powders aerodynamic performance and salbutamol sulfate release rate. Quality target product profile was identified and risk management and principal component analysis were used to guide formulation development. Obtained dry powders for inhalation (DPIs) were evaluated in terms of SLMs size distribution, morphology, true density, drug content, solid state characterization studies, in vitro aerosol performance and in vitro drug release. SLMs micrographs indicated spherical, porous particles. Selected powders showed satisfactory aerosol performance with a mean mass aerodynamic diameter of around 3 μm and acceptable fine particle fraction (FPF). Addition of trehalose positively affected SLMs aerodynamic properties. The results of in vitro dissolution testing indicated that salbutamol sulfate release from the tested SLMs formulations was modified, in comparison to the raw drug release. In conclusion, SLMs in a form of DPIs were successfully developed and numerous factors that affects SLMs properties were identified in this study. Further research is required for full understanding of each factor's influence on SLMs properties and optimization of DPIs with maximized FPFs., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Recently, growing interest is devoted to investigation of bioactive secondary metabolites of endophytic fungi. Thus, as an extension to our previous achievements related to antimicrobial potential of endophytic fungi, Phomopsis species isolated from conifer needles was selected as appropriately promising natural source for drug discovery. Its dichloromethane and ethanol extracts considerably inhibited growth of Escherichia coli and Staphylococcus aureus. Moreover, the individual compounds of dichloromethane extract have been separated, collected and purified using semi preparative liquid chromatographic analysis and comprehensively characterized using mass spectrometry (MS) and nuclear magnetic resonance spectroscopy (NMR). Based on their antimicrobial activity and unique structural characteristics in comparison with well-established drugs from the same therapeutic category, two dominant compounds (Z)-(Z)-2-acetoxyprop-1-en-1-yl-3-(3-((E)-3,4-dihydroxypent-1-en-1-yl)oxiran-2-yl)acrylate (denoted as 325-3) and (Z)-(Z)-2-acetoxyprop-1-en-1-yl 3-(3-((E)-4-hydroxy-3-oxopent-1-en-1-yl)oxiran-2-yl)acrylate (denoted as 325-5) were recognized as valuable leading structures for future discovery of novel antibiotics.

Posterior reversible encephalopathy syndrome (PRES) is an obstetric emergency frequently occurring in a pregnant or puerperal woman, manifested with an acute headache, consciousness impairment, seizures, and visual deficits and is associated with white matter changes predominantly affecting the posterior parietal and occipital lobes of the brain. Apart from the above-described typical location of the changes, the most common atypical location involves the brain stem and basal ganglia. Since magnetic resonance imaging (MRI) is more sensitive and specific imaging technique compared to computerized tomography, establishing the diagnosis and follow-up in patients with PRES is based mainly on MRI findings. It is particularly important not to exclude PRES as a possible diagnosis when we have the appropriate clinical presentation accompanied by the atypical radiological findings, since this clinical-radiological syndrome can often be manifested with an atypical MRI image.

Background/aim: Magnetic resonance imaging (MRI) is a key modality not only for lesion diagnosis, but also to evaluate the extension, type and grade of the tumor. Advanced MRI techniques provide physiologic information that complements the anatomic information available from conventional MRI. The aim of this study was to determine whether there is a correlation between apparent diffusion coefficient (ADC) maps of intracranial glial tumors and histopathologic findings and whether ADCs can reliably distinguish low-grade from high-grade gliomas., Methods: This retrospective study included 25 patients with MRI examination up to seven days before surgery, according to the standard protocol with the following sequences: T1WI, T2WI, FLAIR, DWI and post contrast T1WI. Data obtained from DW MRI were presented by measuring the value of ADC. The ADC map was determined by utilizing Diffusion-Perfusion (DP) Tools software. All the patients underwent surgical resection of the tumor. Histological diagnosis of tumors was determined according to the World Health Organization (WHO) classification. The ADC values were compared with the histopathologic findings according to the WHO criteria., Results: The ADC values of astrocytomas grades I (0.000614 +/- 0.000032 mm2/s) were significantly higher (< 0.001) than the ADC values of anaplastic astrocytomas (0.000436 +/- 0.000016 mm2/s) and the ADC values of glioblastomas multiforme (0.000070 +/- 0.000008 mm2/s). The ADC values of astrocytomas grades II (0.000530 +/- 0.000114 mm2/s) were significantly higher (< 0.001) than the ADC values of anaplastic astrocytomas (0.000436 +/- 0.000016 mm2/s) and glioblastomas multiforme (0.000070 +/- 0.000008 mm2/s). The ADC values of anaplastic astrocy-omas (0.000436 +/- 0.000016 mm2/s) were significantly higher (< 0.001) than the ADC values of glioblastomas multiforme (0.000070 +/- 0.000008 mm2/s). The ADC values in the cystic part of the tumor for astrocytomas grades I (0.000775 +/- 0.000023 mm2/s) were significantly higher (< 0.001) than the ADC values of anaplastic astrocytomas (0.000119 +/- 0.000246 mm2/s) and glioblastomas multiforme (0.000076 +/- 0.000004 mm2/s). The ADC values astrocytomas grades II (0.000511 +/- 0.000421 mm2/s) were significantly higher (< 0.001) than the ADC values of glioblastomas multiforme (0.000076 +/- 0.000004 mm2/s)., Conclusion: DWI with calculation of ADC maps can be regarded as a reliable useful diagnostic tool, which indirectly reflects the proliferation and malignancy of gliomas. The ADCs maps can both predict the results of histopathological tumor and distinguish between low- and high-grade gliomas, and provide significant information for presurgical planning, treatment and prognosis for patients with high-grade astrocytomas.

Inter-laboratory verification of European pharmacopoeia (EP) monograph on derivative spectrophotometry (DS) method and its application for chitosan hydrochloride was carried out on two generation of instruments (earlier GBC Cintra 20 and current technology TS Evolution 300). Instruments operate with different versions of Savitzky-Golay algorithm and modes of generating digital derivative spectra. For resolution power parameter, defined as the amplitude ratio A/B in DS method EP monograph, comparable results were obtained only with algorithm's parameters smoothing points (SP) 7 and the 2nd degree polynomial and those provided corresponding data with other two modes on TS Evolution 300 Medium digital indirect and Medium digital direct. Using quoted algorithm's parameters, the differences in percentages between the amplitude ratio A/B averages, were within accepted criteria (±3%) for assay of drug product for method transfer. The deviation of 1.76% for the degree of deacetylation assessment of chitosan hydrochloride, determined on two instruments, (amplitude (1)D202; the 2nd degree polynomial and SP 9 in Savitzky-Golay algorithm), was acceptable, since it was within allowed criteria (±2%) for assay deviation of drug substance, for method transfer in pharmaceutical analyses., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Infectious bronchitis virus (IBV) is prevalent in all countries with an intensive poultry industry, with the incidence of infection approaching 100% in most locations. Vaccination is only partially successful due to the continual emergence of antigenic variants. At many sites, multiple antigenic types are simultaneously present, requiring the application of multiple vaccines. Although many countries share some common antigenic types, IBV strains within a geographic region are unique and distinct, examples are Europe, the United States of America and Australia. Measures to restrict the introduction of exotic IBV strains should therefore be considered. Infectious bronchitis has a significant economic impact; in broilers, production losses are due to poor weight gains, condemnation at processing and mortality, whilst in laying birds, losses are due to suboptimal egg production and downgrading of eggs. Chickens and commercially reared pheasants are the only natural hosts for IBV. Other species are not considered as reservoirs of IBV. The majority of IBV strains cause tracheal lesions and respiratory disease with low mortality due to secondary bacterial infections, primarily in broilers. Nephropathogenic strains, in addition to tracheal lesions, also induce prominent kidney lesions with mortality of up to 25% in broilers. Strains of both pathotypes infect adult birds and affect egg production and egg quality to a variable degree. Infected chicks are the major source of virus in the environment. Contaminated equipment and material are a potential source for indirect transmission over large distances. Virus is present in considerable titres in tracheal mucus and in faeces in the acute and recovery phases of disease, respectively. Virus spreads horizontally by aerosol (inhalation) or ingestion of faeces or contaminated feed or water. The virus is highly infectious. Clinical signs will develop in contact chicks within 36 h and in nearby sheds within one to two days. Infection is resolved within fourteen days with a rise in antibody titres. In a small number of chicks, latent infection is established with subsequent erratic shedding of virus for a prolonged period of time via both faeces and aerosol. Movement of live birds should be considered as a potential source for the introduction of IBV. Isolation and identification of IBV is needed for positive diagnosis. The preferred method of isolation is to passage a sample in embryonating specified-pathogen-free chicken eggs. Identification is either by monoclonal antibody based enzyme-linked immunosorbent assay (ELISA) or polymerase chain reaction. Virus neutralisation test in tracheal organ culture is the best method for antigenic typing. Continual use of live vaccines complicates diagnosis since no simple diagnostic tool can differentiate a field from a vaccine strain. Nucleotide sequencing of the S1 glycoprotein is the only method to discriminate between all IBV strains. Serology is also complicated by continual use of live vaccines. For surveillance purposes, ELISA is the method of choice, regardless of the antigenic type of IBV involved. The assay is used to monitor the response to vaccination, but field challenge can only be detected if flock antibody status is monitored continually. The antigenic type of a challenge strain involved cannot be ascertained by ELISA.