Understanding the Impacts of Surface Compositions on the In-Vitro Dissolution and Aerosolization of Co-Spray-Dried Composite Powder Formulations for Inhalation

Abstract

Purpose: Dissolution behavior of dry powder inhaler (DPI) antibiotic formulations in the airways may affect their efficacy especially for poorly-soluble antibiotics such as azithromycin. The main objective of this study was to understand the effects of surface composition on the dissolution of spray dried azithromycin powders by itself and in combination with colistin. Methods: Composite formulations of azithromycin (a poorly water-soluble molecule) and colistin (a water-soluble molecule) were produced by spray drying. The resultant formulations were characterized for particle size, morphology, surface composition, solid-state properties, solubility and dissolution. Results: The results demonstrate that surfaces composition has critical impacts on the dissolution of composite formulations. Colistin was shown to increase the solubility of azithromycin. For composite formulations with no surface colistin, azithromycin released at a similar dissolution rate as the spray-dried azithromycin alone. An increase in surface colistin concentration was shown to accelerate the dissolution of azithromycin. The dissolution of colistin from the composite formulations was significantly slower than the spray-dried pure colistin. In addition, FTIR spectrum showed intermolecular interactions between azithromycin and colistin in the composite formulations, which could contribute to the enhanced solubility and dissolution of azithromycin. Conclusions: Our study provides fundamental understanding of the effects of surface concentration of colistin on azithromycin dissolution of co-spray-dried composite powder formulations.

Surface Composition and Aerosolization Stability of an Inhalable Combinational Powder Formulation Spray Dried Using a Three-Fluid Nozzle

“…Concentrations of azithromycin and colistin were determined using the established HPLC methods (29). An Agilent Eclipse Plus (5 μm C18 150 × 4.60 mm) column was used (Agilent, Waldbronn, Germany).…”

“…Surface composition (approximately top 10 nm) of powder formulations was determined using X-ray photoelectron spectroscopy (XPS) (AXIS Ultra DLD spectrometer, Kratos Analytical Inc., Manchester, UK) using the established method (29). Curve-fitting was performed following a Shirley background subtraction using standard procedure in the CasaXPS software with model peaks obtained from pure compounds.…”

Physical stability of dry powder inhaler formulations

“…Recently, a quantitative correlation was established between surface lubricant coverage and aerosolization for carrier-free DPI formulations prepared by co-jet-milling (Mangal et al, 2019). These advanced surface characterization techniques are used more and more frequently to determine the surface composition of excipient or drug particles in dry powder formulations, and are useful for understanding the effects of the particle surface chemical properties on the dissolution and aerosol performance of DPIs [86,107,176,223,224,225].…”

Enhancing Dissolution Rate and Antibacterial Efficiency of Azithromycin through Drug-Drug Cocrystals with Paracetamol

“…Furthermore, the drug exhibits bitter taste [ 22 ] and has been found to be degraded photocatalytically [ 23 ]. A number of approaches like nanoparticles [ 24 , 25 ], nanosuspension [ 26 ], microemulsion [ 27 ], solid dispersion [ 21 , 28 ], co-spray dried composite powder formulation [ 29 ] and metal complexes [ 30 ] have been used to enhance its physicochemical properties of solubility and dissolution. The bitterness of AZT was masked by preparing microparticles [ 31 ] and nanoparticles without affecting dissolution rate [ 32 ].…”