A new powder design method to improve inhalation efficiency of pranlukast hydrate dry powder aerosols by surface modification with hydroxypropylmethylcellulose phthalate nanospheres.
OBJECTIVE
A new particle design method to improve the aerosolization properties of a dry powder inhalation system was developed using surface modification of hydrophobic drug powders (pranlukast hydrate) with ultrafine hydrophilic particles, hydroxypropylmethylcellulose phthalate (HPMCP) nanospheres. The mechanism of the improved inhalation properties of the surface-modified particles and their deposits on carrier particles (lactose) was clarified in vitro.


METHODS
Drug particles were introduced to aqueous colloidal HPMCP dispersions prepared by emulsion-solvent diffusion techniques followed by freeze- or spray-drying of the resultant aqueous dispersions. The surface-modified powders obtained with HPMCP nanospheres and their mixture with lactose powders were aerosolized by Spinhaler and their mode of deposition in lung was evaluated in vitro using a twin impinger. To elucidate the inhalation mechanism of these surface modified particles, we measured their modified micromeritic properties, such as surface topography, specific surface area, dissolution rate, and dispersibility in air.


RESULTS
Dramatically improved inhalation properties of the surface modified powder, i.e. a two-fold increase in emission and a three-fold increase in delivery to deep lung, were found in vitro compared with the original unmodified powder. Improved inhalation was also found with the surface-modified drug deposited on lactose particles. Those improvements were attributed to the increased surface roughness and hydrophilicity of the surface-modified particles, and the resultant increased dispersibility in air.


CONCLUSIONS
Surface modification of hydrophobic drug particles with HPMCP nanospheres to improve hydrophilicity was extremely useful in increasing the inhalation efficiency of the drug itself and the drug deposited on carrier; this was attributed to increased dispersibility in air and emission from the device, for spray- and freeze-dried particles, respectively.
Kawashima
Y
Y
Gifu Pharmaceutical University, Japan. yoshiaki@gifu-pu.ac.jp
Serigano
T
T
Hino
T
T
Yamamoto
H
H
Takeuchi
H
H
D000280:Administration, Inhalation; D000336:Aerosols; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage*; D002867:Chromones / Q000008:administration & dosage*; D003470:Culture Media; D065347:Hypromellose Derivatives; D020024:Leukotriene Antagonists / Q000008:administration & dosage*; D016014:Linear Models; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D008863:Microspheres; D011208:Powders; D013499:Surface Properties; D014867:Water / Q000737:chemistry
D000336:Aerosols; D018927:Anti-Asthmatic Agents; D002867:Chromones; D003470:Culture Media; D020024:Leukotriene Antagonists; D011208:Powders; D014867:Water; D065347:Hypromellose Derivatives; D008747:Methylcellulose; C047681:pranlukast