Co-spray dried hydrophobic drug formulations with crystalline lactose for inhalation aerosol delivery

Spray drying is a rapid method for converting a liquid feed into dried particles for inhalation aerosols. Lactose is a major inhalation excipient used in spray-dried (SD) formulations. However, SD powders produced from solutions are usually amorphous hence unstable to moisture. This problem can potentially be minimized by spray drying a suspension (instead of solution) containing crystalline lactose particles and dissolved drugs. In the present study, the suspension formulation containing dissolved budesonide (BUD) or rifampicin (RIF) and suspended lactose crystals in isopropanol alcohol (IPA) were produced. For comparison, powders were also produced from solution formulations containing the same proportions of drug and lactose dissolved in 50:50 IPA/water as controls. These SD powders were stored at 25 °C/60% RH and 40 °C/75% RH for six months. The particulate properties and in vitro dispersion performance were examined at various storage time points. All powders obtained from spray drying of solutions recrystallized after one week of storage at 25 °C/60% RH. In contrast, SD BUD-lactose obtained from suspension did not change until after three-months of storage when the particle size increased gradually with morphology change and yet the crystallinity remained the same as determined by X-ray powder diffraction. For the SD RIF-lactose obtained from suspension, both particulate properties and in vitro powder dispersion performance showed no significant difference before and after storage at both storage conditions. To conclude, this is the first study to show that SD powder formulations obtained from suspensions containing lactose crystals demonstrated superior storage stability performance, which is desirable for inhaled powders.