Development and Characterization of Excipient Enhanced Growth (EEG) Surfactant Powder Formulations for Treating Neonatal Respiratory Distress Syndrome

• Published in: AAPS PharmSciTech Vol. 22; no. 4; p. 136
• Main Authors: Boc, Susan, Momin, Mohammad A. M., Farkas, Dale R., Longest, Worth, Hindle, Michael
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 15.04.2021
• Subjects: Administration, Inhalation; Aerosols; Biochemistry; Biomedical and Life Sciences; Biomedicine; Biotechnology; Dry Powder Inhalers; Excipients; Humans; Infant, Newborn; Infant, Premature; Leucine - administration & dosage; Particle Size; Pharmacology/Toxicology; Pharmacy; Powders; Research Article; Respiratory Distress Syndrome, Newborn - drug therapy; Surface-Active Agents - administration & dosage; Wettability; leucine; powder aerosol; trileucine; excipient enhanced growth; surfactant
• ISSN: 1530-9932; 1530-9932
• DOI: 10.1208/s12249-021-02001-1

This study aimed to develop and characterize a spray-dried powder aerosol formulation of a commercially available surfactant formulation, Survanta® intratracheal suspension, using the excipient enhanced growth (EEG) approach. Survanta EEG powders were prepared by spray drying of the feed dispersions containing Survanta® (beractant) intratracheal suspension, hygroscopic excipients (mannitol and sodium chloride), and a dispersion enhancer (l-leucine or trileucine) in 5 or 20% v/v ethanol in water using the Buchi Nano Spray Dryer B-90 HP. Powders were characterized for primary particle size, morphology, phospholipid content, moisture content, thermal properties, moisture sorption, and surface activity. The aerosol performance of the powders was assessed using a novel low-volume dry powder inhaler (LV-DPI) device operated with 3-mL volume of dispersion air. At both ethanol concentrations, in comparison to trileucine, l-leucine significantly reduced the primary particle size and span and increased the fraction of submicrometer particles of the Survanta EEG powders. The l-leucine-containing Survanta EEG powders exhibited good aerosolization performance with ≥ 88% of the mass emitted (% nominal) after 3 actuations from the modified LV-DPI device. In addition, l-leucine-containing powders had a low moisture content (< 3% w/w) with transition temperatures close to the commercial surfactant formulation and retained their surface tension reducing activity after formulation processing. A Survanta EEG powder containing l-leucine was developed which showed efficient aerosol delivery from the modified LV-DPI device using a low dispersion air volume.