The cohesive-adhesive balances in dry powder inhaler formulations II: influence on fine particle delivery characteristics.
OBJECTIVE
To investigate the influence of the cohesive-adhesive balances on dry powder formulation aerosolization and delivery characteristics.


METHODS
De-agglomeration properties of pharmaceutical powders were investigated using an Aerosizer at various shear forces. Aerosol drug deposition properties of drug-only formulations and carrier-based formulations were investigated using a low-resistance device (Rotahaler) and a high-resistance device (Turbuhaler) via a twin-stage impinger.


RESULTS
A paradoxical relationship between particle cohesive strength and de-agglomeration efficiencies of drug-only formulations was observed, where an increase in cohesive strength led to a higher fine particle fraction. A possible explanation for the variation in the fluidization and aerosolization properties between low and high cohesive particles was modeled on the relationship between cohesion, metastable agglomerate size, and the resulting aerodynamic drag force acting on the fluidized agglomerates. The addition of a fine particle lactose carrier influenced the drug deposition patterns in different ways depending on the relative cohesive and adhesive force balances within the formulation.


CONCLUSIONS
The use of the colloid Atomic Force Microscrope (AFM) technique in combination with the cohesive-adhesive balance (CAB) system provides a novel preformulation tool for investigating the likely behavior of a dry powder formulation and a possible means of interpreting the possible de-aggregation and dispersion mechanisms of carrier-based formulations.
Begat
Philippe
P
Pharmaceutical Technology Research Group, Department of Pharmacy & Pharmacology, University of Bath, Bath BA2 7AY, United Kingdom.
Morton
David A V
DA
Staniforth
John N
JN
Price
Robert
R
D000268:Adhesiveness; D000280:Administration, Inhalation; D000336:Aerosols; D000420:Albuterol / Q000008:administration & dosage; D001993:Bronchodilator Agents / Q000008:administration & dosage; D019819:Budesonide / Q000008:administration & dosage; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D005079:Excipients; D007785:Lactose; D008855:Microscopy, Electron, Scanning; D009330:Nebulizers and Vaporizers; D010316:Particle Size; D011208:Powders / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet
D000336:Aerosols; D001993:Bronchodilator Agents; D005079:Excipients; D011208:Powders; D019819:Budesonide; D007785:Lactose; D000420:Albuterol