Humidity-induced changes of the aerodynamic properties of dry powder aerosol formulations containing different carriers

Abstract

This paper presents the findings of two related studies. The aim of the first was to study any changes in the aerodynamic properties of salbutamol base powder formulations when different sugars were used as the carriers, after storage at an elevated humidity (75% RH), and whether any such changes (if any) were related to the physical properties of the carriers. The aim of the second was to investigate whether "ageing", i.e. storage of the carrier, drug and blends under desiccation for more than 2 years, affected the aerodynamic properties of salbutamol sulphate powder formulations. Different formulations were prepared, each containing 1.5% (w/w) micronised salbutamol base or sulphate blended with the sieved fraction (63-90 microm) of one of the following sugars: alpha lactose monohydrate, sorbitol, maltose and dextrose. The salbutamol base blends were then stored unprotected at 75% RH (ambient temperature) and salbutamol fine particle fractions (FPFs) were measured by laser diffraction (LD) (% < 5.2 microm) and a multistage liquid impinger (MSLI) (% < 5.3 microm), following aerosolisation at 100 l min(-1) from a model glass inhaler, after storage of each formulation at the elevated conditions for 0, 1 and 6 days. Particle morphology and equilibrium moisture content (EMC) of each formulation prior to and after storage were also evaluated. However, the salbutamol sulphate blends containing either "fresh" or "aged" components were only characterized using LD at 60 l min(-1). Prior to exposure to 75% RH, the lactose blend was found to give the highest FPF of salbutamol (30% by LD and 37% by MSLI), followed by the sorbitol blend (17% by LD and 29% by MSLI), then by the dextrose blend (15% by LD and 25% by MSLI) and finally by the maltose blend (13% by LD and 13% by MSLI). Exposure to 75% RH for 6 days resulted in a small reduction of salbutamol FPF from the lactose blend but drastic diminution of salbutamol FPFs from other blends. After exposure to the high RH, the lactose blend adsorbed ca. 0.4% whilst each of the other sugars took up larger quantities of water (15-40%) and underwent a marked change in the surface texture of the particles. "Ageing" of the carriers and/or formulations did not seem to alter the aerodynamic properties of the drug. "Ageing" of micronised salbutamol sulphate prior to blending, however, was found to improve the FPF of drug. LD was capable of detecting subtle differences between the various formulations and generated FPF results that correlated with those measured by MSLI.