Storage and in-use stability of an excipient enhanced growth (EEG) synthetic lung surfactant powder formulation.

OBJECTIVE: To evaluate the storage and in-use stability of a novel synthetic lung surfactant (SLS) excipient enhanced growth (EEG) powder formulation. SIGNIFICANCE: Aerosol delivery of surfactant formulations could address limitations of current instilled surfactant replacement therapy for neonatal respiratory distress syndrome. A stable surfactant powder formulation is essential for this approach. METHODS: SLS-EEG powder was spray-dried from a formulation of dipalmitoyl -phosphatidylcholine (DPPC), surfactant protein B peptide mimic (B-YL), mannitol, sodium chloride, and l-leucine. Powders were filled into hydroxypropyl methylcellulose (HPMC) capsules and stored in aluminum-aluminum blisters at 25  °C, 5  °C and -20 °C (all ± 2 °C) and 40 ± 5% relative humidity (RH) for 6 months. Physicochemical and aerosol properties were assessed post-spray drying and post-storage. In-use stability was assessed by exposing powders to 22 °C/45% RH for 30 and 120 min and 30 °C/75% RH for 120 min before dry powder inhaler (DPI) actuation. RESULTS: DPPC content remained stable for 6 months at all storage temperatures. Powder morphology and particle size were unchanged at 5 °C and -20 °C, but altered at 25 °C. Solid-state stability and surface activity were unaffected. Emitted doses remained high (>95%) after 3 months using an infant air-jet DPI, though in vitro lung deposition decreased from ∼50% to ∼40% and ∼30% at 3 and 6 months. In-use exposure of the formulation in device to 22 °C/45% RH caused no lung deposition changes, but it declined at 30 °C/75% RH (∼40% vs. ∼50%). CONCLUSIONS: A synthetic lung surfactant EEG powder formulation with physicochemical stability and acceptable aerosol performance up to 6 months storage has been successfully produced.