title: Development of budesonide nanocluster dry powder aerosols: preformulation.
abstract: Wet milling was previously demonstrated as a simple process for producing agglomerates of budesonide nanoparticles (also known as NanoClusters) for use in dry powder aerosol formulation. The resulting budesonide NanoCluster powders exhibited a large emitted fraction and a high fine particle fraction (FPF) from a Monodose® dry powder inhaler. In this work, excipients were added premilling or postmilling and the performance of budesonide NanoCluster dry powders was investigated. Sodium chloride, Pluronic®, or ethanol was added prior to milling due to their ability to modify surface tension or ionic strength and thereby affect the attrition/agglomeration process. Lactose or l-leucine was added after milling because these are known to modify powder flow and dispersion. The chemical stability of budesonide was maintained in all cases, but the physical aerosol properties changed substantially with the addition of excipients. In all cases, the addition of excipients led to an increase in the size of the budesonide NanoClusters and tended to reduce the emitted fraction and FPF. Titrating excipients may provide a means to discretely modify the aerosol properties of budesonide NanoClusters but did not match the performance of excipient-free NanoCluster powder.
authors.affiliation: Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, Kansas 66047, USA.
authors.forename: Nashwa
authors.initials: N
authors.lastname: El-Gendy
authors.forename: Parthiban
authors.initials: P
authors.lastname: Selvam
authors.forename: Pravin
authors.initials: P
authors.lastname: Soni
authors.forename: Cory
authors.initials: C
authors.lastname: Berkland
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D019819:Budesonide / Q000008:administration & dosage / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D004355:Drug Stability; D000431:Ethanol / Q000737:chemistry; D005079:Excipients / Q000737:chemistry; D005938:Glucocorticoids / Q000008:administration & dosage / Q000737:chemistry*; D007785:Lactose / Q000737:chemistry; D007930:Leucine / Q000737:chemistry; D053758:Nanoparticles; D036103:Nanotechnology; D009330:Nebulizers and Vaporizers; D009994:Osmolar Concentration; D010316:Particle Size; D020442:Poloxamer / Q000737:chemistry; D011208:Powders; D012212:Rheology; D012965:Sodium Chloride / Q000737:chemistry; D013499:Surface Properties; D013500:Surface Tension; D013678:Technology, Pharmaceutical / Q000379:methods; D013997:Time Factors
chemical_list: D000336:Aerosols; D005079:Excipients; D005938:Glucocorticoids; D011208:Powders; D020442:Poloxamer; D000431:Ethanol; D012965:Sodium Chloride; D019819:Budesonide; D007930:Leucine; D007785:Lactose