Qu Li, Zhou Qi Tony, Denman John A, Stewart Peter J, Hapgood Karen P, Morton David A V
Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia.
Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN 47907-2091, USA.
Eur J Pharm Sci. 2015 Oct 12;78:264-72. doi: 10.1016/j.ejps.2015.07.016. Epub 2015 Jul 26.
This study investigates the effects of a variety of coating materials on the flowability and dissolution of dry-coated cohesive ibuprofen powders, with the ultimate aim to use these in oral dosage forms. A mechanofusion approach was employed to apply a 1% (w/w) dry coating onto ibuprofen powder with coating materials including magnesium stearate (MgSt), L-leucine, sodium stearyl fumarate (SSF) and silica-R972. No significant difference in particle size or shape was measured following mechanofusion with any material. Powder flow behaviours characterised by the Freeman FT4 system indicated coatings of MgSt, L-leucine and silica-R972 produced a notable surface modification and substantially improved flow compared to the unprocessed and SSF-mechanofused powders. ToF-SIMS provided a qualitative measure of coating extent, and indicated a near-complete layer on the drug particle surface after dry coating with MgSt or silica-R972. Of particular note, the dissolution rates of all mechanofused powders were enhanced even with a coating of a highly hydrophobic material such as magnesium stearate. This surprising increase in dissolution rate of the mechanofused powders was attributed to the lower cohesion and the reduced agglomeration after mechanical coating.
本研究考察了多种包衣材料对干包衣粘性布洛芬粉末流动性和溶出度的影响,最终目的是将其用于口服剂型。采用机械融合法将1%(w/w)的干包衣应用于布洛芬粉末,包衣材料包括硬脂酸镁(MgSt)、L-亮氨酸、富马酸硬脂酸钠(SSF)和二氧化硅-R972。与任何材料进行机械融合后,未检测到粒径或形状有显著差异。由Freeman FT4系统表征的粉末流动行为表明,与未处理的和经SSF机械融合的粉末相比,MgSt、L-亮氨酸和二氧化硅-R972包衣产生了显著的表面改性并显著改善了流动性。飞行时间二次离子质谱(ToF-SIMS)提供了包衣程度的定性测量,并表明在用MgSt或二氧化硅-R972进行干包衣后,药物颗粒表面形成了近乎完整的包衣层。特别值得注意的是,即使使用高度疏水的材料如硬脂酸镁进行包衣,所有机械融合粉末的溶出速率也都提高了。机械融合粉末溶出速率的这种惊人提高归因于机械包衣后内聚力降低和团聚减少。