Alternative sugars as potential carriers for dry powder inhalations.
Most dry powder inhaler (DPI) formulations rely on lactose monohydrate as a carrier in the drug powder blends. However, lactose cannot be used for compounds that interact with the reducing sugar function of the lactose, such as formoterol, budesonide or peptides and proteins. In this study, alternative carriers like mannitol, glucose, sorbitol, maltitol and xylitol have therefore been evaluated for their potential use in DPI formulations. Raw materials were characterised physico-chemically and blends with the model drug substance budesonide were tested with respect to the aerosolization behaviour of the powders. It was found out that similarly to the problems known for lactose monohydrate, such as supplier variability, variability between different qualities of one supplier, the same difficulties apply to the alternative carriers investigated. Different sources and qualities of mannitol led to significant differences in the fine particle fraction (FPF), varying from 15 to 50% for two different qualities of mannitol. Similar observations were made for the other carrier materials studied. Also, the influence of conditioning the raw material at different relative humidity was found to have substantial influence on the performance of drug/carrier blends which is characterised by a strong decrease in the FPF. In summary, mannitol showed potential as a drug carrier to be used in DPIs whereas the more hygroscopic sugars only showed poor dispersibility.
Steckel
Hartwig
H
Department of Pharmaceutics and Biopharmaceutics, Christian Albrecht University Kiel, Gutenbergstrasse 76, Kiel 24118, Germany. steckel@pharmazie.uni-kiel.de
Bolzen
Nina
N
D000280:Administration, Inhalation; D019819:Budesonide / Q000008:administration & dosage / Q000737:chemistry; D002152:Calorimetry, Differential Scanning; D002851:Chromatography, High Pressure Liquid; D004337:Drug Carriers / Q000737:chemistry*; D005947:Glucose / Q000737:chemistry; D008320:Maltose / Q000031:analogs & derivatives* / Q000737:chemistry; D008353:Mannitol / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D009330:Nebulizers and Vaporizers; D010316:Particle Size; D011208:Powders / Q000008:administration & dosage / Q000737:chemistry*; D013012:Sorbitol / Q000737:chemistry; D013402:Sugar Alcohols / Q000737:chemistry; D013549:Sweetening Agents / Q000737:chemistry*; D014993:Xylitol / Q000737:chemistry
D004337:Drug Carriers; D011208:Powders; D013402:Sugar Alcohols; D013549:Sweetening Agents; D008353:Mannitol; D013012:Sorbitol; D019819:Budesonide; D008320:Maltose; C010745:maltitol; D005947:Glucose; D014993:Xylitol