通过多晶型转变为针状晶体（β 型），类固醇 KSR - 592 在体外与 Jethaler 一起改善了吸入行为。

Improved inhalation behavior of steroid KSR-592 in vitro with Jethaler by polymorphic transformation to needle-like crystals (beta-form).

作者信息

Ikegami Kazuhiko, Kawashima Yoshiaki, Takeuchi Hirofumi, Yamamoto Hiromitsu, Isshiki Nobuyuki, Momose Den-Ichi, Ouchi Kiyohisa

机构信息

Pharmaceutical Research Laboratories, Kissei Pharmaceutical Co, Ltd, Nagano, Japan.

出版信息

Pharm Res. 2002 Oct;19(10):1439-45. doi: 10.1023/a:1020492213172.

DOI:10.1023/a:1020492213172

PMID:12425460

Abstract

PURPOSE

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.

METHOD

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%).

CONCLUSION

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.

摘要

目的

本研究的目的是通过改变药物的晶体形状和粒径，以改善甾体KSR-592与乳糖的干粉吸入行为，用于新设计的吸入装置Jethaler。

方法

通过在含5%乙醇的己烷中搅拌α型晶体，使其由原始晶体（α型）多晶型转变为β型，从而改变晶体形状。用双级撞击器和多级冲击器评估所得晶体的体外吸入特性。

结果

通过多晶型转变获得了宽度为1.8微米、长度为41微米的针状晶体（β型），其动力学由阿弗拉米方程描述。负载在乳糖颗粒上的β型晶体在Jethaler产生的气流中易于分离并粉碎成细颗粒，与原始晶体相比，这显著增加了沉积在双级撞击器中的可吸入分数（RF）（43.8%）和多级冲击器的细颗粒分数（FPF）（FPF = 39.3%），原始晶体的相应值分别为RF = 5.8%，FPF = 4.7%。