Inhalable Nanocomposite Microparticles with Enhanced Dissolution and Superior Aerosol Performance.

Abstract

Previous studies have shown that combining colistin (Col), a cationic polypeptide antibiotic, with ivacaftor (Iva), a cystic fibrosis (CF) drug, could achieve synergistic antibacterial effects against Pseudomonas aeruginosa. The purpose of this study was to develop dry powder inhaler formulations for co-delivery of Col and Iva, aiming to treat CF and lung infection simultaneously. In order to improve solubility and dissolution for the water-insoluble Iva, Iva was encapsulated into bovine serum albumin (BSA) nanoparticles (Iva-BSA-NPs). Inhalable composite microparticles of Iva-BSA-NPs were produced by spray-freeze-drying using water-soluble Col as the matrix material and l-leucine as an aerosol enhancer. The optimal formulation showed an irregularly shaped morphology with fine particle fraction (FPF) values of 73.8 ± 5.2% for Col and 80.9 ± 4.1% for Iva. Correlations between "D×ρtapped" and FPF were established for both Iva and Col. The amorphous solubility of Iva is 66 times higher than the crystalline solubility in the buffer. Iva-BSA-NPs were amorphous and remained in the amorphous state after spray-freeze-drying, as examined by powder X-ray diffraction. In vitro dissolution profiles of the selected DPI formulation indicated that Col and Iva were almost completely released within 3 h, which was substantially faster regarding Iva release than the jet-milled physical mixture of the two drugs. In summary, this study developed a novel inhalable nanocomposite microparticle using a synergistic water-soluble drug as the matrix material, which achieved reduced use of excipients for high-dose medications, improved dissolution rate for the water-insoluble drug, and superior aerosol performance.

• Authors: Chune Zhu, Jianting Chen, Shihui Yu, Chailu Que, Lynne S Taylor, Wen Tan, Chuanbin Wu, Qi Tony Zhou
• Journal: Molecular pharmaceutics (Mol Pharm) Vol. 17 Issue 9 Pg. 3270-3280 (09 08 2020) ISSN: 1543-8392 [Electronic] United States
• PMID: 32643939 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Aerosols
• Aminophenols
• Anti-Bacterial Agents
• Excipients
• Powders
• Quinolones
• ivacaftor
• Colistin

Topics

• Administration, Inhalation
• Aerosols (chemistry, pharmacology)
• Aminophenols (chemistry, pharmacology)
• Anti-Bacterial Agents (chemistry, pharmacology)
• Colistin (chemistry, pharmacology)
• Drug Compounding (methods)
• Dry Powder Inhalers (methods)
• Excipients (chemistry)
• Nanocomposites (chemistry)
• Nanoparticles (chemistry)
• Particle Size
• Powders (chemistry, pharmacology)
• Pseudomonas aeruginosa (drug effects)
• Quinolones (chemistry, pharmacology)
• Solubility (drug effects)