Medway School of Pharmacy, University of Kent, Kent, UK.
Int J Pharm. 2010 Jun 15;392(1-2):178-88. doi: 10.1016/j.ijpharm.2010.03.057. Epub 2010 Apr 2.
The aim of the present study was to investigate the effect of crystallising mannitol from different binary mixtures of acetone/water on the resultant physical properties and to determine the effects of any changes on in vitro aerosolisation performance, when the different mannitol crystals were used as a carrier in dry powder inhaler formulations containing salbutamol sulphate. Mannitol particles were crystallised under controlled conditions by dissolving the sugar in water and precipitating the sugar using binary mixtures of acetone/water in different percentages as anti-solvent media. For comparison purposes the physical properties and deposition behaviour of commercially available mannitol were also studied. SEM showed that all crystallised mannitol particles were more elongated than the commercial mannitol. Solid state studies revealed that commercial mannitol and mannitol crystallised using acetone in the presence of 10-25% v/v water as anti-solvent was beta-polymorphic form whereas mannitol crystallised in the presence of a small amount of water (0-7.5%) was the alpha-form. All the crystallised mannitol samples showed poor flowability. Nevertheless, the powdered crystallised mannitol and commercial samples were blended with salbutamol in the ratio 67.5:1. The aerosolisation performance of the formulations containing the engineered mannitol (evaluated using Multi Stage Liquid Impinger) was considerably better than that of the commercial mannitol formulation (the fine particle fraction was increased from 15.42% to 33.07-43.99%, for the formulations containing crystallised mannitol). Generally, carriers having a high tapped density and high fraction of fine carrier particles produced a high FPF. The improvement in the DPI performance could be attributed to the presence of elongated carrier particles with smooth surfaces since these are believed to have less adhesive forces between carrier and the drug resulting in easier detachment of the drug during the inhalation.
本研究的目的是考察从不同丙酮/水二元混合物中结晶甘露醇对所得物理性质的影响，并确定当不同甘露醇晶体用作含有硫酸沙丁胺醇的干粉吸入剂制剂中的载体时，任何变化对体外雾化性能的影响。甘露醇颗粒在控制条件下结晶，将糖溶解在水中，然后使用不同比例的丙酮/水二元混合物作为反溶剂介质沉淀糖。为了比较目的，还研究了商业可得甘露醇的物理性质和沉积行为。SEM 表明，所有结晶甘露醇颗粒都比商业甘露醇颗粒更细长。固态研究表明，商业甘露醇和在丙酮存在下结晶的甘露醇，使用 10-25%v/v 水作为反溶剂是β-多晶型形式，而在少量水（0-7.5%）存在下结晶的甘露醇是α-形式。所有结晶甘露醇样品的流动性都很差。然而，将结晶甘露醇和商业样品与沙丁胺醇以 67.5:1 的比例混合。含有工程甘露醇的制剂（使用多阶段液体撞击器评估）的雾化性能明显优于商业甘露醇制剂（制剂中细颗粒分数从 15.42%增加到 33.07-43.99%）。通常，具有高密度和高比例细载体颗粒的载体产生高 FPF。DPI 性能的提高可归因于存在具有光滑表面的细长载体颗粒，因为据信这些颗粒在载体和药物之间具有较小的粘附力，从而在吸入过程中更容易使药物脱离。
