Chemistry and Drug Delivery Group, Universities of Kent and Greenwich, Kent ME4 4TB, UK.
Colloids Surf B Biointerfaces. 2010 Sep 1;79(2):345-56. doi: 10.1016/j.colsurfb.2010.04.016. Epub 2010 May 5.
In this research mannitol particles were prepared by recrystallisation using non-solvent precipitation technique to investigate the effect of engineered carrier particles on their physicochemical properties and the in vitro deposition profiles of a model drug (salbutamol sulphate (SS)) from a dry powder inhaler (DPI). To this end, mannitol aqueous solution (15%, w/v) was added to different ratios of ethanol:water (100:0, 95:5, 90:10 and 85:15) to obtain mannitol particles. These crystallised mannitol particles were analysed in terms of micromeritic properties, morphology, DSC, FT-IR, and in vitro fine particle fraction (FPF) and emitted dose (ED) of SS. The results showed that the elongation ratio of all the recrystallised mannitol batches was higher than the original material giving them a needle-shaped morphology. Salbutamol sulphate deposition profiles from DPI formulation containing recrystallised needle-shaped mannitol showed enhanced performance and better delivery to the lower MSLI stages. The FPF increased from 15.4+/-1.1 to 45.8+/-0.7% when the commercial mannitol was replaced by mannitol crystallised from ethanol:water (90:10). This improvement could be due to the presence of elongated mannitol crystals in formulation blends. Solid state characterisation of engineered mannitol showed that the commercial mannitol was beta-form, mannitol recrystallised from ethanol:water (85:15) was alpha-form and that samples recrystallised in presence of pure ethanol or other ratios of ethanol:water (95:5 and 90:10) were the mixtures of alpha-, beta- and delta-forms. Multi-solvent recrystallisation technique was proved to have potential to produce mannitol crystals suitable for enhanced aerosolisation efficiency. Comparing different crystallised mannitol formulations showed that the final form (the type of polymorph) of the crystallised mannitol does not have a substantial effect on salbutamol sulphate aerosolisation performance.
在这项研究中，甘露醇颗粒通过非溶剂沉淀技术的重结晶制备，以研究工程载体颗粒对其物理化学性质的影响以及模型药物（硫酸沙丁胺醇（SS））从干粉吸入器（DPI）中的体外沉积分布。为此，将 15%（w/v）的甘露醇水溶液添加到不同比例的乙醇：水（100:0、95:5、90:10 和 85:15）中以获得甘露醇颗粒。对这些结晶甘露醇颗粒进行了微粉学特性、形态、DSC、FT-IR 以及 SS 的体外细颗粒分数（FPF）和发射剂量（ED）分析。结果表明，所有重结晶甘露醇批次的伸长率均高于原始材料，使其具有针状形态。含有重结晶针状甘露醇的 DPI 制剂中硫酸沙丁胺醇的沉积分布显示出增强的性能和更好地输送到较低的 MSLI 阶段。当用乙醇：水（90:10）结晶的甘露醇代替商业甘露醇时，FPF 从 15.4+/-1.1%增加到 45.8+/-0.7%。这种改善可能是由于制剂混合物中存在长形甘露醇晶体。工程甘露醇的固态特性表明，商业甘露醇为β-形式，乙醇：水（85:15）重结晶的甘露醇为α-形式，而在纯乙醇或其他乙醇：水（95:5 和 90:10）比例存在下重结晶的样品为α-、β-和δ-形式的混合物。多溶剂重结晶技术已被证明具有生产适用于增强雾化效率的甘露醇晶体的潜力。比较不同结晶甘露醇制剂表明，结晶甘露醇的最终形式（多晶型物的类型）对硫酸沙丁胺醇雾化性能没有实质性影响。
