Application of co-grinding to formulate a model pMDI suspension.
The objective of this study was to investigate the effect of co-grinding the model drug, triamcinolone acetonide (TAA), with a polymeric surfactant on the in vitro performance of a model pMDI suspension system. The physicochemical properties of TAA after co-grinding with the surfactant, Pluronic F77, were determined by laser light diffraction, helium pycnometry and equilibrium solubility measurements. TAA-surfactant interaction was investigated by differential scanning calorimetry and Fourier transform infrared spectroscopy (FTIR). The suspension characteristics of pMDI formulations prepared with co-ground TAA and surfactant were investigated by determining their in situ sedimentation, rheological profiles and vapor pressure. The performance characteristics of the pMDI formulations were determined by cascade impaction and dose delivery through-the-valve (DDV) measurements. It was found that the presence of Pluronic F77 decreased the solubility of TAA in the propellant medium. Co-grinding TAA particles with Pluronic F77 influenced the particle size distribution, sedimentation and flocculation characteristics of the pMDI suspension formulation. The addition of Pluronic F77 decreased the viscosity of the pMDI formulation. Formulating the suspension pMDI system with co-ground TAA and Pluronic F77 decreased the mass median aerodynamic diameter (MMAD) of the emitted aerosol and increased the percent respirable fraction (%RF). The co-ground TAA and Pluronic F77 pMDI suspension formulation exhibited greater physical stability which was due to the influence of the co-grinding technique on the physicochemical properties of the TAA particle surface and the propellant dispersion medium. The changes induced by co-grinding with Pluronic F77 improved the performance characteristics of a pMDI suspension formulation by stabilizing the suspension and influencing the flocculation characteristics. Co-grinding is a process which may be useful when developing new pMDI systems containing HFA propellants.
Williams
R O
RO
The University of Texas at Austin, College of Pharmacy, Austin 78712-1074, USA. williro@mail.utexas.edu
Repka
M A
MA
Barron
M K
MK
D000280:Administration, Inhalation; D000336:Aerosols; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D005079:Excipients / Q000008:administration & dosage / Q000737:chemistry*; D009330:Nebulizers and Vaporizers; D010316:Particle Size; D020442:Poloxamer / Q000008:administration & dosage / Q000737:chemistry*; D012212:Rheology; D012995:Solubility; D013501:Surface-Active Agents / Q000008:administration & dosage / Q000737:chemistry*; D013535:Suspensions; D014222:Triamcinolone Acetonide / Q000008:administration & dosage* / Q000737:chemistry*; D014835:Volatilization
D000336:Aerosols; D000893:Anti-Inflammatory Agents; D005079:Excipients; D013501:Surface-Active Agents; D013535:Suspensions; D020442:Poloxamer; D014222:Triamcinolone Acetonide