Storage and in-use stability of an excipient enhanced growth (EEG) synthetic lung surfactant powder formulation
Abstract
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
The SLS-EEG powder was prepared via spray drying a formulation containing dipalmitoylphosphatidylcholine (DPPC), surfactant protein B peptide mimic (B-YL), mannitol, sodium chloride, and l-leucine. Powders were packaged in hydroxypropyl methylcellulose (HPMC) capsules and stored in aluminium-aluminium blister packs to protect from moisture ingress at 25 ± 2 °C and 40 ± 5% relative humidity (RH), 5 ± 2 °C and 40 ± 5% RH and −20 ± 2 °C and 40 ± 5% RH for 6 months. Physicochemical properties and aerosol performance were analyzed post-spray drying and after storage. In-use stability was assessed by exposing powders to 22 °C/45% RH for 30 and 120 minutes and 30 °C/75% RH for 120 minutes prior to actuation in a dry powder inhaler (DPI).
Results
DPPC content remained stable up to 6 months at all storage temperatures. Powder morphology and particle size remained unchanged at 5 °C and −20 °C, with some changes at 25 °C. Solid-state stability and surface activity were unaffected by storage. Aerosol performance using a positive-pressure infant air-jet DPI platform showed high emitted doses (>95%) after 3 months, though in vitro lung deposition in a simulated neonatal airway model decreased from ∼50% initially to ∼40% and ∼30% after 3 and 6 months, respectively, of storage. In-use exposure of the formulation in device to 22 °C/45% RH caused no significant lung deposition changes, though delivery efficiency declined with 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.
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Materials
Synthetic DPPC with a purity of >99% and surfactant protein B (SP-B) peptide mimic (B-YL) with a purity of >95% were obtained from Avanti Polar Lipids, Inc. (Alabaster, AL) and CSBio (Menlo Park, CA), respectively (35-36). L-leucine (analytical reagent grade) was purchased from Sigma-Aldrich Chemical Co. (St Louis, MO). Analytical reagent grade sodium chloride, D-mannitol, ammonium formate and HPLC grade ethanol and methanol were procured from Fisher Scientific Co. (Hanover Park, IL).
Momin, M. A. M., Howe, C., Longest, W., & Hindle, M. (2025). Storage and in-use stability of an excipient enhanced growth (EEG) synthetic lung surfactant powder formulation. Drug Development and Industrial Pharmacy, 1–16. https://doi.org/10.1080/03639045.2025.2508845
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