硫酸沙丁胺醇脂质体干粉吸入剂的研制。
Development of liposomal salbutamol sulfate dry powder inhaler formulation.
机构信息
School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China.
出版信息
Biol Pharm Bull. 2010;33(3):512-7. doi: 10.1248/bpb.33.512.
The purpose of our study was to develop a formulation of liposomal salbutamol sulfate (SBS) dry powder inhaler (DPI) for the treatment of asthma. Liposomes of high encapsulation efficiency (more than 80%) were prepared by a vesicular phospholipid gel (VPG) technique. SBS VPG liposomes were subjected to lyophilization using different kinds of cryoprotectants in various mass ratios. Coarse lactose (63-106 microm) in different mass ratios was used as a carrier. Magnesium stearate (0.5%) was added as a lubricator. The dry liposomal powders were then crushed by ball milling and sieved through a 400-mesh sieve to control the mean particle size at about 10 microm. The effects of different kinds of cryoprotectants and the amount of lactose carrier on the fine particle fraction (FPF) of SBS were investigated. The results showed that the developed formulation of liposomal dry powder inhaler was obtained using lactose as a cryoprotectant with a mass ratio of lyophilized powder to carrier lactose at 1 : 5; 0.5% magnesium stearate was used as a lubricator. The value of FPF for SBS was 41.51+/-2.22% for this formulation. Sustained release of SBS from the VPG liposomes was found in the in vitro release study. The study results offer the promising possibility of localized pulmonary liposomal SBS delivery in the anhydrous state.
我们研究的目的是开发一种硫酸沙丁胺醇脂质体(SBS)干粉吸入剂(DPI)用于治疗哮喘。通过囊泡磷脂凝胶(VPG)技术制备了具有高包封效率(超过 80%)的脂质体。使用不同种类的冷冻保护剂以不同的质量比将 SBS VPG 脂质体进行冷冻干燥。以不同质量比的粗乳糖(63-106μm)作为载体。添加硬脂酸镁(0.5%)作为润滑剂。然后通过球磨粉碎干燥的脂质体粉末,并通过 400 目筛筛分,将平均粒径控制在约 10μm。考察了不同种类的冷冻保护剂和乳糖载体的用量对 SBS 的微细粒子分数(FPF)的影响。结果表明,采用乳糖作为冷冻保护剂,冻干粉末与载体乳糖的质量比为 1:5,得到了所开发的脂质体干粉吸入剂的配方;使用 0.5%硬脂酸镁作为润滑剂。对于该配方,SBS 的 FPF 值为 41.51+/-2.22%。在体外释放研究中发现 VPG 脂质体中的 SBS 具有持续释放。研究结果为无水状态下局部肺部脂质体 SBS 传递提供了有希望的可能性。