Improved inhalation behavior of steroid KSR-592 in vitro with Jethaler by polymorphic transformation to needle-like crystals (beta-form).
OBJECTIVE
The aim of the present study was to improve the dry powder inhalation behavior of steroid KSR-592 with lactose by altering the crystal shape and the particle size of the drug for use in a newly designed inhalation device, Jethaler.


METHODS
The shape of the crystals was changed by polymorphic transformation of original crystal (alpha-form) to beta-form by agitating alpha-form crystals in hexane containing 5% ethanol. The inhalation properties of the resultant crystals in vitro were evaluated with a twin impinger and cascade impactor.


RESULTS
Needle-like crystals (beta-form) with dimensions of 1.8 microm in width x 41 microm in length were obtained by the polymorphic transformation, the kinetics of which was described by the Avrami equation. The beta-form crystals loaded on lactose particles were easily separated and crushed into fine particles in the airstream produced in the Jethaler, which increased dramatically the respirable fraction (RF) deposited in the twin impinger (43.8%) and the fine particle fraction (FPF) of the cascade impactor (FPF = 39.3%) compared with their values for the original crystals (RF = 5.8%, FPF = 4.7%).


CONCLUSIONS
The dry powder inhalation properties of steroid KSR-592 (platelike crystal, alpha-form) were improved dramatically by changing the crystal shape to a needle-like shape by the polymorphic transformation to the beta-form.
Ikegami
Kazuhiko
K
Pharmaceutical Research Laboratories, Kissei Pharmaceutical Co, Ltd, Nagano, Japan. kazuhiko_ikegami@pahrm.kissei.co.jp
Kawashima
Yoshiaki
Y
Takeuchi
Hirofumi
H
Yamamoto
Hiromitsu
H
Isshiki
Nobuyuki
N
Momose
Den-Ichi
D
Ouchi
Kiyohisa
K
D000280:Administration, Inhalation; D000731:Androstanes / Q000008:administration & dosage*; D003460:Crystallization; D007785:Lactose / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D009330:Nebulizers and Vaporizers / Q000706:statistics & numerical data; D011208:Powders; D013256:Steroids / Q000008:administration & dosage* / Q000737:chemistry; D014961:X-Ray Diffraction / Q000379:methods
D000731:Androstanes; C473300:KSR592; D011208:Powders; D013256:Steroids; D007785:Lactose