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Respiratory devices such as metered dose inhalers (MDI), nebulizers and dry powder inhalers (DPI) have been used to administer active pharmaceutical ingredients to treat lung diseases. Inhalable drug particles for DPI formulation are conventionally produced by a top down approach through crystallization followed by milling. This approach tends to generate partially amorphous materials that require post-processing to improve the formulations’ stability. Other methods involve homogenization or precipitation and often require the use of stabilizers, mostly surfactants. The purpose of our work was therefore to develop a novel method for preparation of fine drug particles using a microfluidic reactor and to find an appropriate particle isolation method, in this case ultrasonic spray freeze drying, hence avoiding the need of additional homogenization step or use of a stabilizer. Different active pharmaceutical ingredients and excipients were tested for compatibility with budesonide and beclomethasone dipropionate found to be the most appropriate for further characterization. In the final developed method, a commercial T-junction microfluidic reactor was employed to produce the particle suspension (using an ethanol–water, methanol-water and an acetone–water systems), which was directly fed into an ultrasonic atomization probe, followed by direct feeding to liquid nitrogen. Freeze drying was the final step in the process. The result were fine crystalline budesonide and beclomethasone dipropionate powders that were characterized by the following analytical techniques: optical microscopy, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), dynamic light scattering (DLS), dynamic vapor sorption (DVS), thermal gravimetric analysis (TGA), X-ray powder diffraction (XRD) and aerosol performance with Next Generation Impactor (NGI). When blended with lactose and dispersed using an Aerolizer at 100 L/min air flow rate, budesonide generated fine particle fraction in the range 47.6±2.8% to 54.9±1.8%, thus exhibiting a good aerosol performance. Drug product formulations were compared to commercially available products and showed comparable aerosol performance. Subsequent sample analysis confirmed the suitability of the developed method to produce inhalable drug particles without additional homogenization or stabilizers. The developed method provides a general viable solution for particle isolation from microfluidic reactor. Pri zdravljenju pljučnih bolezni učinkovine običajno doziramo z uporabo inhalacijskih naprav kot so inhalatorji pod tlakom (MDI), inhalatorji s suhim prahom (DPI) in nebulatorji. Običajno se delci za DPI formulacije pripravljajo s “top-down” pristopom, kjer s kristalizacijo in nato mletjem dosežemo ustrezno velikost delcev. S tem pristopom običajno dobimo amorfen material, ki za izboljšanje fizikalne stabilnosti potrebuje dodatne tehnološke korake. Druge sorodne tehnike vsebujejo homogenizacijo ali obarjanje in običajno zahtevajo uporabo stabilizatorjev oziroma površinsko aktivnih snovi. Namen našega dela je bil razviti novo metodo za pripravo delcev za inhaliranje z uporabo mikrofluidnega reaktorja, hkrati pa poiskati primerno metodo za izolacijo teh delcev. Sušenje z razprševanjem in zamrzovanjem se je izkazalo za najbolj primerno, saj smo se na ta način lahko izognili uporabi dodatne homogenizacije in uporabe stabilizatorjev. Med testiranimi učinkovinami in ekscipienti, sta se kot najprimernejša izkazala Budezonid in Beklometazon dipropionat. Metoda izdelave delcev je vsebovala komercialno dostopen mikrofluidni reaktor s T-stikom (uporabili smo etanolno-vodni, metanolno-vodni ter aceton-vodni sistem), ki je bil neposredno sklopljen z ultrazvočno šobo za razprševanje, usmerjeno v čašo s tekočim dušikom. Sušenje z razprševanjem in zamrzovanjem je predstavljalo zadnji procesni korak. Pridobljene mikronizirane delce smo analizirali z mnogimi analitskimi tehnikami kot: optična mikroskopija, vrstična elektronska mikroskopija (SEM), diferenčna dinamična kalorimetrija (DSC), dinamično sipanje svetlobe (DLS), dinamična sorpcija pare (DVS), termogravimetrija (TGA), rentgenska praškovna difrakcija (XRD) in določanje aerodinamskih lastnosti z NGI. Pripravili smo DPI formulacijo tako pripravljenega budezonida in komercialne laktoze, ter jo z uporabo Aerolizerja pri pretoku zraka 100 L/min analizirali z NGI. Delež delcev z aerodinamičnim premerom manjšim od 5 μm je bi med 47.6±2.8% in 54.9±1.8%, kar je pomenilo dobre aerodinamske lastnosti za inhalacije. Izdelane formulacije so bile primerjane s komercialno dostopnimi izdelki in izkazale podobne aerodinamske lastnosti kot referenčni izdelki. Analize so potrdile primernost nove metode za izdelavo delcev, ki se lahko uporabijo v inhalacijah brez dodatne homogenizacije ali stabilizatorjev. Razvita metoda izolacije je prav tako splošno uporabno rešitev za izolacijo delcev v mikrofluidiki.

Background The aim of this study was to determine the incidence of steroid-induced hyperglycaemia (SIH) in patients hospitalised at the tertiary centre for lung diseases, to assess glycaemic control during hospitalisation, and to determine the factors associated with the control of SIH. Methods A 4-month retrospective study was conducted. All patients who received systemic glucocorticoids for ≥ 2 days during hospitalisation, with ≥ 2 elevated blood glucose (BG) readings, were included in the analysis. SIH control was determined by mean BG levels, the number and proportion of elevated and pronouncedly elevated BG readings, and the number of hypoglycaemic events. Results 60 of 283 patients (21.2%) developed SIH, of which 55 patients were included in further analysis. Mean fasting and daytime BG levels were 7.8 ± 2.9 mmol/l and 10.9 ± 2.2 mmol/l, respectively. 41/55 patients (74.5%) had elevated average BG levels. 45/55 patients (81.8%) had > 5 readings or > 20% of all readings exceeding hyperglycaemia threshold, and 33/55 patients (60.0%) had pronouncedly elevated BG levels on more than one occasion. 6/55 patients (10.9%) experienced more than one hypoglycaemic event or a severe hypoglycaemia. Only 9/55 patients (16.4%) achieved adequate SIH control according to all defined criteria. Pre-existing diabetes and longer duration of hospital treatment with low glucocorticoid dose were significantly associated with poorer glycaemic control (p

COPD is a complex, heterogeneous condition. Even in the early clinical stages, COPD carries a significant burden, with breathlessness frequently leading to a reduction in exercise capacity and changes that correlate with long-term patient outcomes and mortality. Implementation of an effective management strategy is required to reduce symptoms, preserve lung function, quality of life, and exercise capacity, and prevent exacerbations. However, current clinical practice frequently differs from published guidelines on the management of COPD. This review focuses on the current scientific evidence and expert opinion on the management of moderate COPD: the symptoms arising from moderate airflow obstruction and the burden these symptoms impose, how physical activity can improve disease outcomes, the benefits of dual bronchodilation in COPD, and the limited evidence for the benefits of inhaled corticosteroids in this disease. We emphasize the importance of maximizing bronchodilation in COPD with inhaled dual-bronchodilator treatment, enhancing patient-related outcomes, and enabling the withdrawal of inhaled corticosteroids in COPD in well-defined patient groups.