Freeze-dried mannitol for superior pulmonary drug delivery via dry powder inhaler.
OBJECTIVE
To show for the first time the superior dry powder inhaler (DPI) performance of freeze dried mannitol in comparison to spray dried mannitol and commercial mannitol.


METHODS
Different mannitol powders were sieved to collect 63-90 μm particles and then analyzed in terms of size, shape, surface morphology, solid state, density, flowability. Salbutamol sulphate-mannitol aerosol formulations were evaluated in terms of homogeneity, SS-mannitol adhesion, and in vitro aerosolization performance.


RESULTS
Freeze dried mannitol demonstrated superior DPI performance with a fine particle fraction believed to be highest so far reported in literature for salbutamol sulphate under similar protocols (FPF = 46.9%). To lesser extent, spray dried mannitol produced better aerosolization performance than commercial mannitol. Freeze dried mannitol demonstrated elongated morphology, α-+β-+δ- polymorphic forms, and poor flowability whereas spray dried mannitol demonstrated spherical morphology, α-+β- polymorphic forms, and excellent flowability. Commercial mannitol demonstrated angular morphology, β- polymorphic form, and good flowability. Freeze dried mannitol demonstrated smoother surface than spray dried mannitol which in turn demonstrated smoother surface than commercial mannitol. FPF of SS increased as mannitol powder porosity increase.


CONCLUSIONS
Freeze drying under controlled conditions can be used as a potential technique to generate aerodynamically light mannitol particles for superior DPI performance.
Chemistry and Drug Delivery Group, Medway School of Pharmacy, University of Kent, ME4 4TB, Kent, UK. waseemkaialy@hotmail.co.uk
Waseem
W
Kaialy
Ali
A
Nokhodchi
D000280:Administration, Inhalation; D000336:Aerosols / Q000737:chemistry*; D000420:Albuterol / Q000008:administration & dosage*; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D058995:Dry Powder Inhalers; D005612:Freeze Drying; D008168:Lung / Q000378:metabolism; D008353:Mannitol / Q000737:chemistry*; D010316:Particle Size; D011208:Powders
D000336:Aerosols; D001993:Bronchodilator Agents; D004337:Drug Carriers; D011208:Powders; D008353:Mannitol; D000420:Albuterol