Dissolution testing for inhalers were previously conducted either on unfractionated drug-carrier powders or drug of specific aerodynamic particle size. In this study, the collection of the full fine particle fraction (FPF) was attempted on a single stage. Capsules containing 30 mg of 2% salbutamol sulfate (SS) was tested to have a FPF of 9 ± 1% using the full set of Andersen cascade impactor (ACI) and a modified Rotahaler® capable of achieving 4.0 kPa pressure drop at 60 L/min air flow rate. A truncated ACI comprising the USP throat, pre-separator, stage 0, stage 4, stage F, polytetrafluoroethylene funnel (TF) and small collection plate (sCP) was found to be capable of achieving a FPF of 9% collected on TF and sCP. An adhesive tape was used to collect the FPF from the TF and sCP and held in place by an enhancer cell in a 200 mL round bottom vessel containing 50 mL Gamble's solution with 0.2 v/v, % Tween 80. Dissolution testing of SS and Seretide® showed burst release of SS and salmeterol while sustained release of fluticasone. This study demonstrated a reproducible method which may be used for evaluation of the full FPF of orally inhaled products.

The novel, easy-to-use, breath-actuated fluticasone propionate/salmeterol multidose dry powder inhaler (MDPI) (AirDuo RespiClick®) was recently approved in the USA for twice-daily treatment of asthma in patients aged ≥ 12 years. This inhaled corticosteroid (ICS) and long-acting β2-adrenoreceptor agonist (LABA) combination treatment is available in low-, mid- and high-dosage formulations (55/14, 113/14 and 232/14 μg, respectively). In 12-week, phase III trials in patients aged ≥ 12 years with persistent asthma, all three dosages of fluticasone propionate/salmeterol MDPI treatment produced significant improvements in lung function and other asthma symptoms compared with fluticasone propionate MDPI monotherapy or placebo MDPI. In a 26-week, phase III trial in this patient population, mid- and high-dosage fluticasone propionate/salmeterol MDPI were noninferior to mid- (250/50 μg) and high- (500/50 μg) dosage fluticasone propionate/salmeterol DPI (Advair Diskus®), respectively, in terms of improvements in lung function. Treatment-emergent adverse events (TEAEs) with fluticasone propionate/salmeterol MDPI were mostly of mild to moderate severity, with no severe TEAEs deemed to be treatment related. Although long-term pharmacovigilance is required to fully establish its safety, given the ease of use and favorable characteristics of the device and its clinical efficacy at relatively low metered doses of the active moieties, fluticasone propionate/salmeterol MDPI is an important emerging treatment option in patients aged ≥ 12 years with asthma.

The in-vitro aerosol performance of two combination dry powder inhaler (DPI) products, Foster® NEXThaler® and Seretide® Diskus® were investigated with single particle aerosol mass spectrometry (SPAMS). The in-vitro pharmaceutical performance is markedly different for both inhalers. Foster® NEXThaler® generates a higher fine particle fraction (FPF <5 μm) and a much higher relative extra fine particle fraction (eFPF <2 μm). In terms of the composition of the aerodynamic particle size distribution (APSD), it could be verified with SPAMS that overall Foster® NEXThaler® emits a significantly higher number of fine and extra fine particles with a median aerodynamic diameter (MAD) of 2.1 μm while Seretide® Diskus® had a larger MAD of 3.1 μm. Additionally, the interactions between the two active pharmaceutical ingredients (APIs) in both products are different. While Seretide® Diskus® emits a significant (37%) number of co-associated API particles, only a negligible number of co-associated API particles were found in Foster® NEXThaler® (<1%). A major difference with Foster® NEXThaler® is that it contains magnesium stearate (MgSt) as a second excipient besides lactose in a so-called 'dual excipient' platform. The data generated using SPAMS suggested that nearly all of the beclomethasone dipropionate particles in Foster® NEXThaler® also contain MgSt and must therefore be co-associated with this additional excipient. This may help explain why beclomethasone dipropionate in Foster® NEXThaler® forms less particle co-associations with the second API, formoterol fumarate, shows a lower cohesive strength in respect to beclomethasone itself and why both APIs exhibit superior detachment from the carrier as evidenced by the increased eFPF and smaller MAD.