High dose spray-dried powders for treating tuberculosis
Mohammad Abdul Motalib Momin, Shubhra Sinha, Ian G Tucker & Shyamal C Das
School of Pharmacy, University of Otago, 18 Frederick Street, P.O. Box 56, Dunedin 9054, New Zealand
Summary
High dose delivery of drugs to the lung using a dry powder inhaler (DPI) is an emerging approach to treat tuberculosis and other respiratory infections. To achieve a high dose in the lung, a highly aerosolizable powder is required which is often difficult for a hygroscopic drug. This study was designed to develop powders of a hygroscopic drug with surfaces enriched in the hydrophobic material by manipulating the spray-drying conditions and to investigate the effect of hydrophobic surface enrichment on aerosolization and stability of the hygroscopic drug. Using a 23 full factorial design, inhalable size (3.1 to 3.9 µm) composite powders of kanamycin (hygroscopic drug) and rifampicin (hydrophobic drug) were produced by varying three spray drying conditions: drug ratio, co-solvent composition and inlet temperature. The powders were wrinkled, flake-shaped and amorphous. Hydrophobic surface enrichment was significantly affected by co-solvent composition as confirmed by X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (ToFSIMS). Increase in hydrophobic surface enrichment (from 80.8 to 100%) increased aerosolization (from 48.0 to 77.2% fine particle fraction- FPF) determined using a Next Generation Impactor (NGI) and decreased density. The composite powders were stable at 15% and 43% RH and 25 ± 2°C during one-month storage in an open Petri dish, and non-toxic (up to 50 µg/mL) to human alveolar and bronchial cell-lines. This systematic study has reported the manipulation of spray-drying conditions for hydrophobic surface enrichment in composite powder particles. Surface enrichment of kanamycin by hydrophobic rifampicin improved aerosolization and stability. The surface modification approach by
