Optimization of a Dry Powder Inhaler Formulation of Nacystelyn, a New Mucoactive Agent

Abstract

Abstract The aim of this study was to optimize a dry powder inhaler formulation containing a new mucoactive drug, nacystelyn. Formulations were made using three types of lactose, crystalline α-lactose, spray-dried lactose and a roller-dried anhydrous β-lactose. The roller-dried anhydrous β-lactose possessed the most adequate surface properties, resulting in a significantly higher (P < 0.05) in-vitro lung deposition of nacystelyn than the conventional crystalline α-lactose and spray-dried lactose. The particle size distribution of roller-dried α-lactose was optimized also. Within the size ranges tested (63–100, 90–125 and 100–160 μm), the coarser the lactose, the higher the in-vitro deposition of the drug (up to 40%). In contrast, the in-vitro lung deposition of 100–160 μm roller-dried β-lactose was very low (< 0.5%), so limiting the potential risk of lung irritation due to the carrier. The influence of the ratio of active ingredient/excipient (w/w) was also investigated. No difference was observed for mixtures from 1:2 to 1:4 while higher dilutions (1:5 and 1:6) showed significantly (P < 0.005) lower deposition results. Finally, the influence of the airflow rate was assessed. No dependence of the fine particle dose was observed between 40 and 80 L min−1 while significantly higher results were obtained at 100 L min−1. The dry powder inhaler formulation of nacystelyn using the unusual roller-dried anhydrous β-lactose resulted in very high and reproducible in-vitro deposition results. However, the latter needs to be confirmed by in-vivo studies.