Core-shell particles for the dispersion of small polar drugs and biomolecules in hydrofluoroalkane propellants.
OBJECTIVE
Demonstrate the applicability of a novel particle-based technology for the development of suspensions of small polar drugs and biomolecules in hydrofluoroalkane (HFA) propellants for pressurized metered-dose inhalers (pMDIs).


METHODS
Emulsification diffusion was used to prepare core-shell particles. The shell consisted of oligo(lactide) grafts attached onto a short chitosan backbone. The active drug was arrested within the particle core. Colloidal Probe Microscopy (CPM) was used to determine the cohesive forces between particles in a model HFA propellant. The aerosol characteristics of the formulations were determined using an Anderson Cascade Impactor (ACI). Cytotoxicity studies were performed on lung epithelial and alveolar type II cells.


RESULTS
CPM results indicate that particle cohesive forces in liquid HFA are significantly screened in the presence of the polymeric shell and correlate well with the physical stability of suspensions in propellant HFA. The proposed formulation showed little or no cytotoxic effects on both Calu-3 and A549 cells.


CONCLUSIONS
Core-shell particles with a shell containing the lactide moiety as the HFA-phile showed excellent dispersion stability and aerosol characteristics in HFA-based pMDIs. This is a general strategy that can be used for developing novel suspension pMDIs of both small polar drugs and large therapeutic molecules.
Wu
Libo
L
Department of Chemical Engineering and Materials Science, Wayne State University, Detroit, Michigan, USA.
Bharatwaj
Balaji
B
Panyam
Jayanth
J
da Rocha
Sandro R P
SR
D000336:Aerosols; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D003102:Colloids; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000008:administration & dosage*; D009330:Nebulizers and Vaporizers; D005466:Fluorocarbons
D000336:Aerosols; D003102:Colloids; D006845:Hydrocarbons, Fluorinated; C094049:apaflurane; D005466:Fluorocarbons