Physicochemical and Aerosolization Performance Stability of an Excipient Enhanced Growth (EEG) Synthetic Lung Surfactant Powder Formulation
Mohammad A.M. Momin1, Connor Howe2, Worth Longest2 & Michael Hindle1
1Department of Pharmaceutics, Virginia Commonwealth University, Richmond, VA 23298, USA
2Department of Mechanical & Nuclear Engineering, Virginia Commonwealth University, Richmond, VA 23298, USA
Neonatal respiratory distress syndrome (NRDS) remains one of the single major causes of infant death. Surfactant replacement therapy (SRT) is the standard therapy for infants with NRDS. However, there are delivery issues associated with liquid bolus instillation which could be eliminated by aerosol delivery of the surfactant formulation. This study aims to characterize the stability of a novel synthetic lung surfactant excipient enhanced growth (EEG) powder formulation. The synthetic lung surfactant EEG powder aerosol formulation was prepared by spray drying a feed dispersion containing the phospholipid, dipalmitoylphosphatidylcholine (DPPC), a surfactant protein B mimic (B-YL), hygroscopic excipients (mannitol and sodium chloride) and a dispersion enhancer (l-leucine). Powders were packaged in hydroxypropyl methylcellulose (HPMC) capsules and stored in Aluminium-Aluminium blister packs. The physicochemical properties and aerosol performance of the powders were characterized immediately following spray drying and after 3 months storage at 25±2°C, 5±2°C and −20±2°C. No significant differences were observed in the DPPC content of the powders after 3-month storage at the three storage temperatures. The micrometer sized powder remained unchanged following storage at 5°C and -20°C, with a small increase in primary particle size observed at 25°C. There were no changes observed in the surface activity of the powder formulation following storage at 25°C and 5°C. Following 3 months storage, the emitted dose (>95%) from a novel dry powder inhaler (DPI) remained unchanged. There was a small decrease in in vitro lung deposition in a simulated neonatal airway model from ~50% initially to ~40% following storage under all conditions.
A synthetic lung surfactant EEG powder has been successfully produced and evaluated following storage and under in-use conditions. The powder appeared stable and its in vitro aerosol performance to a simulated neonatal lung remained acceptable for this challenging route.