Inhalable, Spray-Dried Terbinafine Microparticles for Management of Pulmonary Fungal Infections: Optimization of the Excipient Composition and Selection of an Inhalation Device

Terbinafine is a broad-spectrum antifungal agent with therapeutic potential against pulmonary aspergillosis. The main aim of the current study was to investigate the potential of l-leucine, alone and in combination with mannitol, to improve the performance of spray-dried terbinafine microparticles for inhalation. The study also aimed to investigate the potential of the low resistance Cyclohaler® and the high resistance Handihaler® as inhalation devices for spray-dried microparticles. To this end, eight powder inhalation formulations of terbinafine were prepared by nano spray drying via a factorial experimental design. The formulations were evaluated in vitro for their potential to deliver the antifungal drug to the lungs using the Cyclohaler® and the Handihaler®. Leucine was superior as an excipient to mannitol and to mixtures of leucine and mannitol. Using leucine as an excipient resulted in formulations with fine particle fractions of up to 60.84 ± 0.67% w/w and particle mass median aerodynamic diameters of down to 1.90 ± 0.20 μm, whereas using mannitol as an excipient resulted in formulations with fine particle fractions of up to 18.75 ± 3.46% w/w and particle mass median aerodynamic diameters of down to 6.79 ± 0.82 μm. When leucine was used as an excipient, using 50% w/w rather than 25% w/w ethanol in water as a spray solvent enhanced the dispersibility of the particles, with a mean absolute increase in the formulation fine particle fraction of 9.57% w/w (95% confidence interval = 6.40–12.73% w/w). This was potentially underlain by enrichment of the particle surfaces with leucine. The Cyclohaler® outperformed the Handihaler® as an inhalation device for the developed formulations, with a mean absolute increase in the fine particle fraction of 9.17% w/w (95% confidence interval = 8.17–10.16% w/w).

Obtaining and research of pharmaceutical properties of antiemetics in a form of powder for inhalation

Samples of antiemetic drugs (ondansetronum, palonosetronum, metoclopramidum) in the form of powder for inhalation have been developed by the method of spray drying. The granulometric composition, hygroscopicity and aerodynamic distribution of aerosol particles of the drugs have been investigated. The dosage form of the powder for inhalation of antiemetics (ondansetronum and palonosetronum) in terms of its particle size distribution, hygroscopicity and content of the agent corresponds to those for inhalation using dry powder inhalers. In the study of the phase-dispersed composition of aerosol, ondansetronum and palonosetronum in the dosage form of powder for inhalation as part of the HandiHaler inhaler (at a flow rate of 60 l / min) showed high rates of the released dose up to 72-76%, respirable particle fraction (up to 5 m) up to 54 -56% and a mass median particle size of about 3 microns. Obtaining the inhaled form of metoclopramide requires optimization of the production method for receiving the product with acceptable pharmaceutical properties.

Effect of significant weight loss on disease activity: reason to implement this non-pharmaceutical intervention in daily clinical practice

Obesity is very common in patients with inflammatory rheumatic diseases (IRDs), of which between 27% and 37% of patients have a body mass index ≥30 kg/m2. In addition to further increasing the risk of developing cardiovascular diseases (CVDs) in this group of patients, obesity is associated with higher disease activity and a lower response to drug therapy. This case series showed that in those patients with rheumatoid arthritis or psoriatic arthritis with a substantial weight loss of >10% of body mass, median Disease Activity Score 28 joints score decreased with 0.9. This reduction in disease activity resulted in an increase in the percentage of patients achieving remission from 6% to 63%. This reduction in disease activity was obtained without intensification of medical treatment in 87% of the patients. This case series supports the current evidence that weight reduction has positive effects on the course of the disease and thus also on the CVD risk profile in these patients. Therefore, weight loss can serve as a non-pharmacological treatment option in obese patients with IRDs.

Investigation of the distribution of particles of drugs with the help of cascade impactor

BACKGROUND. Successful nebulization is a result of joint usage of nebulizer and medication, which equally define availability and disposition of the active substance. Amount of the substance delivered by different nebulizer systems may differ in more than 10 times. OBJECTIVE. The aim of the study was to investigate the distribution of aerosol particles of drugs for inhalation manufactured by «Yuria-Pharm» under conditions of usage of Ulaizer Home. MATERIALS AND METHODS. We investigated Ulaizer Home nebulizer and medications for inhalation (Decasan, Lorde hyal, Nebufluson, Nebutamol) with the help of new generation impactor (“Copley Scientific Limited”, Great Britain). RESULTS AND DISCUSSION. Mass median aerodynamic diameter (MMAD) of Decasan particles was 4.878 µm, geometric standard deviation (GSD) – 1.72. MMAD of Lorde hyal particles was 3.194 µm, GSD – 1.556. Drop distribution for Nebutamol was alike the distribution for non-viscous aqueous solutions (MMAD – 5.363 µm, GSD – 1.924). For Nebufluson MMAD was 5.491 µm, GSD – 1.724. CONCLUSIONS. The delivery of the inhaled drug to the required area of the respiratory system is a key to successful nebulization. It directly depends on the parameters of the aerosol. The distribution of particles of drugs manufactured by «Yuria-Pharm» in case of nebulization using Ulaizer Home allows to deliver the required amount of drug to the predefined parts of the respiratory system.

Characterization of Aerosol Nebulized by Aerogen Solo Mesh Nebulizer

Nebulizers are commonly used devices for inhalation treatment of various disorders. There are three main categories of medical nebulization technology: jet nebulizers, ultrasound nebulizer, and mesh nebulizer. The mesh nebulizers seem to be very promising since this technology should be able to produce aerosol with precisely determined particle size and is easy to use as well [1]. Aerosol generated from the mesh nebulizer Aerogen Solo was measured in this work. Particle size distribution with a mass median of aerodynamic diameter (MMAD) was determined by two different methods.

XXL Survey groups and clusters in the Hyper Suprime-Cam Survey. Scaling relations between X-ray properties and weak lensing mass

ABSTRACT Scaling relations trace the formation and evolution of galaxy clusters. We exploited multi-wavelength surveys – the XXL survey at XMM-Newton in the X-ray band, and the Hyper Suprime-Cam Subaru Strategic Program for optical weak lensing – to study an X-ray selected, complete sample of clusters and groups. The scalings of gas mass, temperature, and soft-band X-ray luminosity with the weak lensing mass show imprints of radiative cooling and active galactic nucleus feedback in groups. From the multi-variate analysis, we found some evidence for steeper than self-similar slopes for gas mass ($\beta _{m_\text{g}|m}=1.73 \pm 0.80$) and luminosity (βl|m = 1.91 ± 0.94) and a nearly self-similar slope for the temperature (βt|m = 0.78 ± 0.43). Intrinsic scatters of X-ray properties appear to be positively correlated at a fixed mass (median correlation factor $\rho _{X_1X_2|m}\sim 0.34$) due to dynamical state and merger history of the haloes. Positive correlations with the weak lensing mass (median correlation factor $\rho _{m_\text{wl}X|m}\sim 0.35$) can be connected to triaxiality and orientation. Comparison of weak lensing and hydrostatic masses suggests a small role played by non-thermal pressure support ($9\pm 17{{\ \rm per\ cent}}$).

Investigation of the Quantity of Exhaled Aerosols Released into the Environment during Nebulisation

Background: Secondary inhalation of medical aerosols is a significant occupational hazard in both clinical and homecare settings. Exposure to fugitive emissions generated during aerosol therapy increases the risk of the unnecessary inhalation of medication, as well as toxic side effects. Methods: This study examines fugitively-emitted aerosol emissions when nebulising albuterol sulphate, as a tracer aerosol, using two commercially available nebulisers in combination with an open or valved facemask or using a mouthpiece with and without a filter on the exhalation port. Each combination was connected to a breathing simulator during simulated adult breathing. The inhaled dose and residual mass were quantified using UV spectrophotometry. Time-varying fugitively-emitted aerosol concentrations and size distributions during nebulisation were recorded using aerodynamic particle sizers at two distances relative to the simulated patient. Different aerosol concentrations and size distributions were observed depending on the interface. Results: Within each nebuliser, the facemask combination had the highest time-averaged fugitively-emitted aerosol concentration, and values up to 0.072 ± 0.001 mg m−3 were recorded. The placement of a filter on the exhalation port of the mouthpiece yielded the lowest recorded concentrations. The mass median aerodynamic diameter of the fugitively-emitted aerosol was recorded as 0.890 ± 0.044 µm, lower the initially generated medical aerosol in the range of 2–5 µm. Conclusions: The results highlight the potential secondary inhalation of exhaled aerosols from commercially available nebuliser facemask/mouthpiece combinations. The results will aid in developing approaches to inform policy and best practices for risk mitigation from fugitive emissions.

Clinical Characteristics and Surgical Treatment for Inguinal Endometriosis in Young Women of Reproductive Age

Aim: To study the characteristics and surgical treatment of inguinal endometriosis (IEM), which can occur in women of reproductive age. Methods: Patients who underwent groin surgery at the Hiroshima City Funairi Citizens Hospital between 2004 and 2017 were retrospectively examined. Patients with IEM were divided into 3 groups based on the site of occurrence as follows: at a hernia sac or hydrocele of Nuck’s canal (type I), round ligament (type II), or subcutaneous area (type III). Clinical characteristics were compared among groups. Results: Of 2,798 patients investigated, 28 were pathologically diagnosed as having IEM with 15, 10, and 3 classified as type I, II, and III respectively. All patients presented with a mass (median 20 mm) and/or bulge that mainly occurred at the right inguinal region. Sixteen patients presented with inguinal pain associated with menstruation. While the groups did not differ in terms of most clinical characteristics, the lack of a preoperative diagnosis of IEM occurred more frequently for type I than for types II and III. Conclusions: Because IEM-type I might be underdiagnosed preoperatively, complete resection of a hernia sac or hydrocele of Nuck’s canal with subsequent pathological examination is required for women of reproductive age with an inguinal disease.