In vitro investigation of drug particulates interactions and aerosol performance of pressurised metered dose inhalers.
OBJECTIVE
To determine a relationship between adhesive and cohesive inter-particulate forces of interactions and in vitro performance in pressurised metered dose inhalers (pMDIs) suspension formulations.


METHODS
Interparticulate forces of salbutamol sulphate (SS), budesonide (BUD) and formoterol fumarate dihydrate (FFD) were investigated by in situ atomic force microscopy (AFM) in a model propellant 2H, 3H perfluoropentane (HPFP). Experimental data were analysed using the recently developed cohesive/adhesive analysis method (CAB) and compared with in vitro deposition performances in pMDIs systems using Andersen cascade impactor (ACI).


RESULTS
The in vitro investigation suggested that the micronised drug materials had significantly different aerosolisation profiles when manufactured as single or combination formulations. In general, the greatest significant differences were observed between SS single drug and SS-BUD and SS-FFD combinations. Analysis of the in vitro performance for the SS only formulation suggested that the cohesive nature of SS (as predicted by the CAB and observed with AFM) led to tightly bound flocs that did not fully deaggregate upon aerosolisation.


CONCLUSIONS
It is suggested that the relationship between interparticulate interactions and in vitro performance of pMDIs suspension systems, when compared to direct measurement of the adhesion/cohesion forces, indicated good correlation. This approach may be useful in expediting the development of pMDI formulation and predicting performance.
Traini
Daniela
D
Advanced Drug Delivery Group, Faculty of Pharmacy (A15), University of Sydney, Sydney, NSW, 2006, Australia.
Young
Paul M
PM
Rogueda
Philippe
P
Price
Robert
R
D000268:Adhesiveness; D000335:Aerosol Propellants; D000336:Aerosols; D000420:Albuterol / Q000008:administration & dosage / Q000737:chemistry; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000737:chemistry; D019819:Budesonide / Q000008:administration & dosage / Q000737:chemistry; D002498:Centrifugation; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D004983:Ethanolamines / Q000008:administration & dosage / Q000737:chemistry; D000068759:Formoterol Fumarate; D036501:Metered Dose Inhalers; D018625:Microscopy, Atomic Force; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000737:chemistry*; D013535:Suspensions
D000335:Aerosol Propellants; D000336:Aerosols; D001993:Bronchodilator Agents; D004983:Ethanolamines; D004364:Pharmaceutical Preparations; D013535:Suspensions; D019819:Budesonide; D000420:Albuterol; D000068759:Formoterol Fumarate