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 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.