Production of salbutamol sulfate for inhalation by high-gravity controlled antisolvent precipitation

The purpose of this study was to produce salbutamol sulfate (SS) as a model anti-asthmatic drug using high-gravity controlled precipitation (HGCP) through antisolvent crystallisation. An aqueous solution of SS was passed through a HGCP reactor with isopropanol as antisolvent to induce precipitation. Spray drying was employed to obtain dry powders. Scanning electron microscopy, X-ray powder diffraction (XRD), density measurement, thermal gravimetric analysis, and dynamic vapour sorption were carried out to characterise the powder physical properties. The aerosol performance of the powders was measured using an Aeroliser connected to a multiple stage liquid impinger operating at 60 L/min. The HGCP SS particles were elongated with 0.1 mu m in width but varying length of several mu m, which formed spherical agglomerates when spray dried. The particles showed the same XRD pattern and true density (1.3 g/cm(3)) as the raw material, indicating that they belonged to the same crystalline form. However, the spray dried agglomerates had a much lower tapped density (0.1 g/cm(3)) than the raw material (0.6 g/cm(3)). Compared with the powder obtained by spray drying directly from an aqueous solution, the SS powders obtained from HGCP were much less hygroscopic (0.6% versus 10% water uptake at 90% RH). The in vitro aerosol performance showed a fine particle fraction FPFloaded and FPFemitted up to 54.5 +/- 4.9% and 71.3 +/- 10.0%, respectively. In conclusion, SS powder with suitable physical and aerosol properties can be obtained through antisolvent HGCP followed by spray drying. (c) 2006 Elsevier B.V. All rights reserved.