Preparation of high-performance ultrafine budesonide particles for pulmonary drug delivery

Abstract

Drug particle physical properties are critical for the efficiency of a drug delivered to the lung. Budesonide, as one of the inhaled glucocorticosteroids, is widely used in the treatment of asthma by pulmonary delivery. The purpose of this study was to produce high-performance ultrafine budesonide particles suitable for inhalation using high pressure homogenization (HPH) combined with spray drying (SD). An aqueous suspension of budesonide was passed through a high pressure homogenizer to prepare submicron particles, and SD was employed to obtain dry powders. The effects of HPH and SD process parameters such as pressure, cycle time, initial particle size and concentration were explored. The results indicated that the initial budesonide particles with a volume median diameter (VMD) of 640 nm could be achieved after HPH of 1000 bar and 60 cycle times, and low-density porous spherical budesonide agglomerates with a VMD of 2.90 μm could be generated after spray drying of 1.0% 640 nm (VMD) particle concentration. The as-prepared agglomerates had the same stable crystalline structure as the commercial budesonide product. In vitro evaluation with an Aerolizer inhaler and a multistage liquid impinger (MSLI) showed that they had an excellent aerosol performance, achieving high FPFloaded and FPFemitted values of 42 ± 2% and 81 ± 3%. The technique may be applicable for the production of other high-performance pharmaceutical products for inhalation.