Abberger Thomas, Seo Anette, Schaefer Torben
Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innsbruck, Austria.
Int J Pharm. 2002 Dec 5;249(1-2):185-97. doi: 10.1016/s0378-5173(02)00530-6.
This study was performed in order to evaluate the effects of binder droplet size and powder particle size on agglomerate formation and growth in fluid bed spray agglomeration using a meltable binder. Three different lactose grades, 100, 125 or 350 mesh, were agglomerated using polyethylene glycol (PEG) 3000 at two different concentrations, 11.5 or 22% (volume/mass), and three spray droplet sizes, 30, 60 or 90 microm were applied. The ratio of droplet size/particle size was found to determine whether the mechanism of nucleation was distribution or immersion. Distribution was promoted by a low ratio, whereas immersion was promoted by a high ratio. Distribution as nucleation mechanism led to a more open agglomerate structure and immersion to a denser structure. When the nucleation phase was terminated, coalescence between rewetted nuclei or agglomerates was the growth mechanism with both preceding mechanisms of nucleation. A larger particle size of the lactose led to larger agglomerates. The difference in the effect on growth between the 30 and 60 microm droplets was generally low. The 90 microm droplets at 22% binder concentration offered a potential for uncontrollable growth giving rise to markedly larger agglomerates and a lower reproducibility than 30 and 60 microm droplets.
本研究旨在评估在使用可熔性黏合剂的流化床喷雾团聚过程中，黏合液滴尺寸和粉末颗粒尺寸对团聚体形成和生长的影响。使用三种不同粒度等级的乳糖，100目、125目或350目，在两种不同浓度（体积/质量）的聚乙二醇（PEG）3000下进行团聚，并采用三种喷雾液滴尺寸，30微米、60微米或90微米。发现液滴尺寸与颗粒尺寸的比值决定了成核机制是分布成核还是浸没成核。低比值促进分布成核，而高比值促进浸没成核。作为成核机制的分布成核导致团聚体结构更疏松，而浸没成核导致结构更致密。当成核阶段结束时，再润湿的核或团聚体之间的聚并是两种先前成核机制下的生长机制。乳糖颗粒尺寸越大，团聚体越大。30微米和60微米液滴对生长的影响差异通常较小。在黏合剂浓度为22%时，90微米的液滴会导致生长不可控，从而产生明显更大的团聚体，且与30微米和60微米的液滴相比，重现性更低。
