Aerosolization behavior of carrier-free L-leucine coated salbutamol sulphate powders.

ABSTRACT

Aerosolization behavior of carrier-free l-leucine coated salbutamol sulphate inhalable powders has been studied. L-Leucine coatings were formed by physical vapour deposition (PVD) on the surface of the spherical particles in the gas phase. While depositing L-leucine formed pointy crystalline asperities whose size and density increased with the increased content of L-leucine in the gas phase. The asperity size changed from few nanometers to hundreds of nanometers. Due to the rough surface, all these coated fine powders were well-flowable and could be fed without the aid of coarser carriers. The aerosolization characteristics of the powders were studied with 'Inhalation Simulator' under ascending and fast inhalation profiles. When detected on-line by infrared light attenuation, the emission of the coated powders from an inhaler (Easyhaler) was distinctively dependent on the inhalation flow rate less than 30 l/min whereas that of micronized salbutamol sulphate powder solely depended on the studied inhalation flow rate range up to 100 l/min. Gravimetric measurements showed that emitted doses (ED) and fine particle fractions (FPF) of the coated powders were 5.1-7.1 mg/dose and 42-47%, respectively, which were 3-4 times higher than those of the micronized powder. The ED and FPF of the coated powders decreased as the surface roughness increased which is hypothesized as mechanical interlocking between the surface asperities.