Effect of Inhaler Parameters on the Aerosol Performance of D-LAK Peptide/Capreomycin Co-spray Dried Powder for Pulmonary Delivery
Zitong Shao1, Shing Fung Chow1 and Jenny K.W. Lam1，2,*
1Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicines, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong SAR, China
2 Department of Pharmaceutics, UCL School of Pharmacy, University College London, UK
D-LAK120-A peptide is a synthetic peptide with anti-tuberculosis (TB) activity. Capreomycin is a second-line antibiotic combating drug-resistant Mycobacterium tuberculosis (Mtb). Previous study suggested that D-LAK120-A peptide could potentiate the efficacy of capreomycin when they are used in combination. In this study, a total of eight D-LAK120-A peptide/capreomycin co-spray dried powder formulations were developed with different drug content and mass ratios. The aerosol performance of the combined powder formulations was first evaluated using the next generation impactors (NGI) with Breezhaler® at a flow rate of 90 L/min. All formulations had a similar emitted fraction (EF) of around 80% and fine particle fraction (FPF) of 40~45%. The drug content and mass ratios between two anti-TB agents have no impact on the powder aerosol performance. The aerosol performance of formulation A1 (0.5% capreomycin and 2% D-LAK120-A (w/w)) was further evaluated using three different inhalers, namely Breezhaler®, High-resistance Osmohaler® (HR-Osmohaler®) and Handihaler® at different operation flowrates. This combined formulation showed flowrate-dependent EF and FPF. The best powder dispersion was achieved with HR-Osmohaler® operated at a flow rate of 50 L/min, with an EF of around 65% and the FPF of over 50%. This dispersion condition facilitates powder emission and simultaneously avoids excessive impaction on the throat, resulting in better particle distribution and higher FPF.
Different inhalers and airflow rates affected the aerosol performance of the D-LAK120-A peptide/capreomycin co-spray dried powder formulations. The use of HR-Osmohaler® at a flow rate of 50 L/min resulted in the best aerosol performance of the co-spray dried formulation.