Traini D, Young P M, Rogueda P, Price R
Pharmaceutical Surface Science Research Group, Department of Pharmacy, University of Bath, Bath BA2 7AY, United Kingdom.
Int J Pharm. 2006 Aug 31;320(1-2):58-63. doi: 10.1016/j.ijpharm.2006.04.016. Epub 2006 May 5.
Colloid probe atomic force microscopy (AFM) was utilised to quantify the cohesive forces of salbutamol sulphate in a model non-pressurised fluorinated liquid (mHFA), in the presence of increasing concentrations of poly(ethylene glycol) (PEG; molecular weight (MW) 200, 400 and 600). In addition, samples of PEG 400 (0.05-0.5%, v/w), were analysed in the presence of 0.001% (w/w) of poly(vinyl pyrrolidone) (PVP). In the absence of any stabilizing agents, strong attractive forces were present between particles. Increasing the concentration of the different MW PEG solutions in the mHFA system (up to 0.5%, v/w), significantly decreased the force of interaction (ANOVA, p<0.05). The decrease in cohesion was particularly evident at very low concentrations of PEG (0.05-0.1%, v/w). Further data analysis (p<0.05) suggested that the reduction in the force of cohesion was dependent on the concentration and molecular weight of PEG. The addition of low concentration of PVP to the PEG 400-mHFA system had the most significant influence on drug particle cohesion. In the presence of PVP, increasing addition of PEG 400 (0.05-0.5%, v/w) to the mHFA, resulted in no significant reduction in the force of cohesion (p>0.05). Clearly, an understanding of the conformation of polymer molecules at interfaces is of vital importance when controlling the stability/flocculation behaviour of sterically stabilized pMDI suspensions. In this context, the use of the colloid probe AFM technique has provided a quantitative insight into the interactions of these complex systems and may be an invaluable asset during the early phase of formulation product development.
使用胶体探针原子力显微镜（AFM）在模型非加压氟化液体（mHFA）中，在聚乙二醇（PEG；分子量（MW）200、400和600）浓度不断增加的情况下，对硫酸沙丁胺醇的内聚力进行定量分析。此外，在0.001%（w/w）的聚乙烯吡咯烷酮（PVP）存在下，对PEG 400（0.05 - 0.5%，v/w）的样品进行分析。在没有任何稳定剂的情况下，颗粒之间存在强烈的吸引力。在mHFA系统中增加不同分子量PEG溶液的浓度（高达0.5%，v/w），显著降低了相互作用力（方差分析，p<0.05）。在非常低的PEG浓度（0.05 - 0.1%，v/w）下，内聚力的降低尤为明显。进一步的数据分析（p<0.05）表明，内聚力的降低取决于PEG的浓度和分子量。向PEG 400 - mHFA系统中添加低浓度的PVP对药物颗粒内聚力影响最为显著。在PVP存在的情况下，向mHFA中增加PEG 400（0.05 - 0.5%，v/w）的添加量，内聚力没有显著降低（p>0.05）。显然，在控制空间稳定的pMDI悬浮液的稳定性/絮凝行为时，了解聚合物分子在界面处的构象至关重要。在此背景下，胶体探针AFM技术的使用为这些复杂系统的相互作用提供了定量见解，并且在制剂产品开发的早期阶段可能是一项宝贵的资产。
