Controlled Surface Roughness of Nano-Matrices Improves Aerosol Performance
PHILIP CHI LIP KWOK (1), Amolnat Tunsirikongkon (2), William Glover (3), Hak-Kim Chan (1)
(1) Faculty of Pharmacy, The University of Sydney, Camperdown, NSW 2006, Australia, (2) Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand, (3) GSK Consumer Health, 82 Hughes Avenue, Ermington, NSW 2115, Australia
Abstract Number: 129
Preference: Platform Presentation
Last modified: April 22, 2010
Working Group: Aerosol Drug Delivery
Objective: To control the surface roughness of nano-matrices and test its effect on aerosol performance.
Materials and Methods: Aqueous lysozyme solutions were poured into isopropanol during high-shear mixing to produce nanoparticles by anti-solvent precipitation. The size of the nanoparticles was varied by adjusting the lysozyme concentration and water-to-isopropanol volume ratio. The resultant suspensions were spray dried to obtain micron-sized aggregates (termed nano-matrices). Laser diffraction was used for measuring the aggregate size distribution. Smooth particles were obtained by spray drying lysozyme solution. Surface roughness was quantified as the root mean square (RMS) roughness by atomic force microscopy. The aerosol performance was assessed by dispersing 10 mg of powder from a Rotahaler® into a Next Generation Impactor at 60 L/min of air flow for 4 s. Ultraviolet spectrophotometry was used to assay the lysozyme deposits throughout the impactor (n = 3).
Results and Discussion: The size distributions of the smooth lysozyme particles and rough nano-matrices were comparable, with volume median diameters of about 1 micro-metre. Surface roughness increased with the size of the primary nanoparticles. The root mean square surface roughness ranged from 21.5 – 53.8 nano-metre. The fine particle dose (FPD) was defined as the total mass of particles < 4.46 micro-metre and the fine particle fraction (FPF) loaded was the quotient of the FPD and the dose loaded into the inhaler. The FPF loaded increased linearly with increasing surface roughness, possibly due to reduced cohesion. The linear correlation equation was FPF = 1.11 × (RMS roughness) – 21.28, with the coefficient of determination = 0.95.
Conclusions: Smooth lysozyme particles and rough nano-matrices with comparable size distributions were successfully produced. The surface roughness of the aggregates was controlled by varying the size of the primary nanoparticles. The aerosol performance was shown to improve with increasing surface roughness.