Storage and in-use stability of an excipient enhanced growth (EEG) synthetic lung surfactant powder formulation
Year: 2025
Type: article
Abstract: ObjectiveTo evaluate the storage and in-use stability of a novel synthetic lung surfactant (SLS) excipient enhanced growth (EEG) powder formulation.SignificanceAerosol 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.MethodsThe 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).ResultsDPPC 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%).ConclusionsA synthetic lung surfactant EEG powder formulation with physicochemical stability and acceptable aerosol performance up to 6 months storage has been successfully produced.
Authors: Mohammad A. M. Momin, Connor Howe, Worth Longest, Michael Hindle
Institution: Virginia Commonwealth University
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Awards: Virginia Commonwealth University - to develop Synthetic Lung Surfactant Formulations and Delivery Devices for Treating Infants with respiratory distress syndrome in Low Resource Envi..., Virginia Commonwealth University - to identify alternative drug formulation and manufacturing methods for a novel, inhalational synthetic surfactant for treatment of infants with Res..., Preclinical development of a synthetic lung surfactant dry powder aerosol for hypoxemia or acute respiratory distress syndrome patients receiving different modes of ventilation support
OpenAlex ID: W4410537698