Institute of Nanotechnology and Bioengineering, School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston, PR1 2HE, UK.
College of Pharmacy, Hawler Medical University, Erbil, Iraq.
AAPS PharmSciTech. 2018 Jul;19(5):2434-2448. doi: 10.1208/s12249-018-1058-4. Epub 2018 Jun 5.
Proliposome formulations containing salbutamol sulphate (SS) were developed using spray drying, and the effects of carrier type (lactose monohydrate (LMH) or mannitol) and lipid to carrier ratio were evaluated. The lipid phase comprised soy phosphatidylcholine (SPC) and cholesterol (1:1), and the ratios of lipid to carrier were 1:2, 1:4, 1:6, 1:8 or 1:10 w/w. X-ray powder diffraction (XRPD) revealed an interaction between the components of the proliposome particles, and scanning electron microscopy (SEM) showed that mannitol-based proliposomes were uniformly sized and spherical, whilst LMH-based proliposomes were irregular and relatively large. Using a two-stage impinger (TSI), fine particle fraction (FPF) values of the proliposomes were higher for mannitol-based formulations, reaching 52.6%, which was attributed to the better flow properties when mannitol was used as carrier. Following hydration of proliposomes, transmission electron microscopy (TEM) demonstrated that vesicles generated from mannitol-based formulations were oligolamellar, whilst LMH-based proliposomes generated 'worm-like' structures and vesicle clusters. Vesicle size decreased upon increasing carrier to lipid ratio, and the zeta potential values were negative. Drug entrapment efficiency (EE) was higher for liposomes generated from LMH-based proliposomes, reaching 37.76% when 1:2 lipid to carrier ratio was used. The in vitro drug release profile was similar for both carriers when 1:6 lipid to carrier ratio was used. This study showed that spray drying can produce inhalable proliposome microparticles that can generate liposomes upon contact with an aqueous phase, and the FPF of proliposomes and the EE offered by liposomes were formulation-dependent.
采用喷雾干燥法制备硫酸沙丁胺醇前体脂质体，考察载体种类（一水乳糖（LMH）或甘露醇）和脂质与载体比例对前体脂质体的影响。脂质相由大豆卵磷脂（SPC）和胆固醇（1:1）组成，脂质与载体的比例为 1:2、1:4、1:6、1:8 或 1:10（w/w）。X 射线粉末衍射（XRPD）显示前体脂质体颗粒的各成分之间存在相互作用，扫描电子显微镜（SEM）显示甘露醇基前体脂质体粒径均匀且呈球形，而 LMH 基前体脂质体不规则且相对较大。采用两段撞击式分级收集器（TSI），甘露醇基制剂的前体脂质体的微细粒子分数（FPF）值较高，达到 52.6%，这归因于甘露醇作为载体时具有更好的流动性能。前体脂质体水合后，透射电子显微镜（TEM）显示甘露醇基制剂生成的囊泡为寡层囊泡，而 LMH 基前体脂质体生成“蠕虫状”结构和囊泡聚集体。随着载体与脂质比例的增加，囊泡粒径减小，zeta 电位值为负值。采用 1:2 的脂质与载体比例时，LMH 基前体脂质体生成的脂质体的药物包封效率（EE）较高，达到 37.76%。当采用 1:6 的脂质与载体比例时，两种载体的体外药物释放曲线相似。本研究表明，喷雾干燥法可制备可吸入前体脂质体微球，与水相接触时可生成脂质体，前体脂质体的 FPF 和脂质体的 EE 均取决于制剂。
