Surface energy and interparticle forces correlations in model pMDI formulations.
OBJECTIVE
To compare experimental measurements of particle cohesion and adhesion forces in a model propellant with theoretical measurements of the interfacial free energy of particulate interactions; with the aim of characterizing suspension stability of pressurized metered dose inhalers (pMDIs).


METHODS
Interparticulate forces of salbutamol sulfate, budesonide, and formoterol fumarate dihydrate were investigated by in situ atomic force microscopy (AFM) in a model propellant 2H,3H perfluoropentane. The surface thermodynamic properties were determined by contact angle (CA) and inverse gas chromatography (IGC). Experimental data were compared with theoretical work of adhesion/cohesion using a surface component approach (SCA), taking into account both dispersive and polar contributions of the surface free energy.


RESULTS
Results indicated that the measured forces of interaction between particles in model propellant could not be accounted for by theoretical treatment of the dispersive surface free energies via CA and IGC. A correlation between theoretical work of adhesion/cohesion and AFM measurements was observed upon the introduction of the polar interfacial interactions within the SCA model.


CONCLUSIONS
It is suggested that the polar contributions of the surface free energy measurements of particles may play a crucial role in particle interaction within propellant-based systems. Together with the application of a SCA model, this approach may be capable of predicting suspension stability of pMDI formulations.
Traini
Daniela
D
Pharmaceutical Technology Research Group, Department of Pharmacy, University of Bath, Bath, UK. r.price@bath.ac.uk
Rogueda
Philippe
P
Young
Paul
P
Price
Robert
R
D000420:Albuterol / Q000032:analysis; D019819:Budesonide / Q000032:analysis; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002849:Chromatography, Gas / Q000379:methods; D004983:Ethanolamines / Q000032:analysis; D005466:Fluorocarbons / Q000032:analysis / Q000737:chemistry; D000068759:Formoterol Fumarate; D007834:Lasers; D008027:Light; D036501:Metered Dose Inhalers; D018625:Microscopy, Atomic Force / Q000379:methods; D008855:Microscopy, Electron, Scanning / Q000379:methods; D010316:Particle Size; D011208:Powders; D055672:Static Electricity; D013499:Surface Properties / Q000187:drug effects*; D013678:Technology, Pharmaceutical / Q000379:methods; D013816:Thermodynamics; D010420:Pentanes
D000420:Albuterol; D019819:Budesonide; D004983:Ethanolamines; D005466:Fluorocarbons; D000068759:Formoterol Fumarate; D011208:Powders; C008806:perfluoropentane; D010420:Pentanes