Background: When inhaling medication, it is essential that drug particles are delivered to all sites of lung inflammation, including the peripheral airways. The aim of this study was to assess the lung deposition and lung distribution of beclomethasone dipropionate (BDP)=formoterol (100=6 mg), both dissolved in hydrofluoroalkane (HFA) and delivered by pressurized metered dose inhaler (pMDI) in healthy subjects, asthmatic, and chronic obstructive pulmonary disease (COPD) patients, to investigate how the in vitro characteristics of the formulation translate into the in vivo performance in diseases with different airway obstruction.

Individuals with a 1 -antitrypsin (AAT) deficiency and cystic fibrosis (CF) have a protease-antiprotease imbalance in their lungs, which leads to early onset progressive lung disease. Inhalation of AAT may restore protective levels in the lungs. This study aimed to determine the efficiency of delivering AAT using a novel inhalation device in subjects with AAT deficiency and CF compared with healthy subjects.In total, 20 subjects (six healthy, seven with AAT deficiency and seven with CF) inhaled ,70 mg of radiolabelled active AAT, with controlled breathing patterns adjusted to lung function. Postinhalation, total and regional lung deposition and extrathoracic deposition of radiolabelled AAT were measured.Total lung deposition of AAT was ,70% of the filling dose. The magnitude of deposition was similar in all treatment groups, with no adverse effect on lung function or any influence of disease severity on total lung deposition.Inhalation with controlled breathing patterns using the AKITA 2 device (lung function adapted) leads to high total lung deposition regardless of the degree of lung function impairment. Delivery of large amounts of AAT was achieved in a short period of time. This device may be an ideal option for aerosol therapy.

Higher bioavailability of magnesium citrate as compared to magnesium oxide shown by evaluation of urinary excretion and serum levels after single-dose administration in a randomized cross-over study AbstractBackground: The development of several disorders, such as cardiovascular diseases, diabetes and osteoporosis, has been linked to suboptimal dietary magnesium (Mg) intake. In this context, a number of studies have tried to investigate which Mg compounds are best suited for Mg supplementation. Results suggest that organic Mg compounds are superior to the inorganic Mg oxide in terms of bioavailability, but a reliable statement cannot yet be made due to systematic differences in the applied study designs.Methods: This single-center, randomized, open, 2-period, 2-supplementation, 2-sequence, single-dose, cross-over study was conducted in 20 healthy male subjects of Caucasian origin to investigate and compare the bioavailability of Mg citrate, an organic Mg compound, and Mg oxide, an inorganic Mg compound. In order to reliably assess the bioavailability of both Mg compounds, subjects were supplemented with magnesium to saturate their Mg-pools before administration of each study product. The bioavailability of both Mg compounds was then assessed by measurement of the renally eliminated Mg quantity during an interval of 24 h after single-dose Mg administration (A e 0-24h ) as primary endpoint. Additionally, the Mg concentrations in a subset of leukocytes, in erythrocytes and in serum were measured on an exploratory basis.Results: After administration, A e 0-24h of magnesium was higher for Mg citrate than for Mg oxide. A e 0-24h for both study products was compared by analysis of variance (ANOVA), revealing an adjusted mean difference of 0.565 mmol, which was statistically significant at the 5% level (95% confidence interval of 0.212 to 0.918 mmol, p = 0.0034

Background: This study evaluated the lung deposition and the distribution pattern in the airways of a fixed combination of beclometasone dipropionate (BDP) and formoterol fumarate (FF) (100/6 μg) delivered as an extrafine dry powder formulation (mass median aerodynamic diameter, MMAD (μm) BDP = 1.5; FF = 1.4) through the NEXThaler® device in healthy subjects, asthmatics, and patients with COPD.Methods: Healthy subjects (n = 10), asthmatic patients (n = 9; 30%≤FEV1 < 80%), and COPD patients (n = 9; FEV1/FVC ≤70%, 30%≤FEV1 < 50%) completed this open-label, single administration (inhalation of four actuations) parallel group study. After inhalation of 99mTc-radiolabeled BDP/FF combination (radiolabeled BDP + unlabeled FF), the drug deposition was assessed using a gamma-scintigraphy technique. Patients' lung function was assessed.Results: No significant difference in drug deposition was observed between the three study groups. Mean lung deposition, extrathoracic deposition, and amount exhaled ranged, respectively, between 54.9% and 56.2%, between 41.8% and 43.2%, and between 1.6% and 3.3% of BDP emitted dose (71.7 ± 2.5 μg) for the three study groups. The central to peripheral ratio (reflecting the lung distribution pattern) ranged between 1.23 and 2.02 for the three study groups, indicating a distribution of the drug throughout the airways, including periphery. The study treatment produced a forced expiratory volume in one second (FEV1) increase over time, reaching a maximum improvement generally within 1–4 hours.Conclusions: The fixed extrafine dry powder combination BDP/FF (100/6 μg) administered through the DPI NEXThaler® achieved similar intrapulmonary deposition in healthy subjects, in asthmatic patients, and COPD patients (approximately 55% of emitted dose) irrespective of the underlying lung disease with a negligible amount of exhaled particles. The study showed high reliability of the device, reproducible dosing, and distribution throughout the lungs. The results supported the concept of efficient delivery of the combination to the target pulmonary regions, thanks to the extrafine formulation. FEV1 profile confirmed a relevant pharmacodynamic effect of the product.

The new liposomal CsA PARI formulation can be deposited to the peripheral lung using the PARI eFlow nebulizer. The treatment was well tolerated, and no drug-related side effects were observed. Once or twice daily dosing of 10 mg CsA A PARI would result in a sufficient peripheral lung deposition of approximately 14 and 28 mg/week, respectively.