Chemistry and Drug Delivery Group, Medway School of Pharmacy, University of Kent, ME4 4TB Kent, UK.
Int J Pharm. 2012 Feb 28;423(2):184-94. doi: 10.1016/j.ijpharm.2011.12.018. Epub 2011 Dec 17.
The purpose of this study was to evaluate the relationships between physicochemical properties and aerosolisation performance of different grades of lactose. In order to get a wide range of physicochemical properties, various grades of lactose namely Flowlac 100 (FLO), Lactopress anhydrous 250 (LAC), Cellactose 80 (CEL), Tablettose 80 (TAB), and Granulac 200 (GRA) were used. The different lactose grades were carefully sieved to separate 63-90 μm particle size fractions and then characterised in terms of size, shape, density, flowability, and solid state. Formulations were prepared by blending each lactose with salbutamol sulphate (SS) at ratio of 67.5:1 (w/w), and then evaluated in terms of SS content uniformity, lactose-SS adhesion properties, and in vitro aerosolisation performance delivered from the Aerolizer. Sieved lactose grades showed similar particle size distributions (PSDs) and good flow properties but different particle shape, particle surface texture, and particle solid state. Content uniformity assessments indicated that lactose particles with rougher surface produced improved SS homogeneity within DPI formulation powders. Lactose-SS adhesion assessments indicated that lactose particles with more elongated shape and the rougher surface showed smaller adhesion force between lactose and salbutamol sulphate. Lactose powders with higher bulk density and higher tap density produced smaller emission (EM) and higher drug loss (DL) of SS. In vitro aerosolisation for various lactose grades followed the following rank order in terms of deposition performance: GRA>TAB>LAC ≈ CEL>FLO. Linear relationships were established showing that in order to maximize SS delivery to lower airway regions, lactose particles with more elongated shape, more irregular shape, and rougher surface are preferred. Therefore, considerable improvement in DPI performance can be achieved by careful selection of grade of lactose included within DPI formulations.
本研究旨在评估不同等级乳糖的物理化学性质与气溶胶化性能之间的关系。为了获得广泛的物理化学性质，使用了各种等级的乳糖，即 Flowlac 100（FLO）、Lactopress 无水 250（LAC）、Cellactose 80（CEL）、Tablettose 80（TAB）和 Granulac 200（GRA）。将不同等级的乳糖仔细过筛，分离出 63-90μm 的粒径级分，然后在粒径、形状、密度、流动性和固体状态方面进行表征。将每种乳糖与硫酸沙丁胺醇（SS）按 67.5:1（w/w）的比例混合制成制剂，然后从 Aerolizer 评估 SS 含量均匀性、乳糖-SS 粘附特性和体外气溶胶化性能。过筛的乳糖等级具有相似的粒径分布（PSD）和良好的流动性，但具有不同的颗粒形状、颗粒表面纹理和颗粒固体状态。含量均匀性评估表明，表面较粗糙的乳糖颗粒可提高 DPI 制剂粉末中 SS 的均匀度。乳糖-SS 粘附评估表明，形状更细长、表面更粗糙的乳糖颗粒之间的粘附力较小。具有较高堆密度和较高振实密度的乳糖粉末会导致 SS 的发射（EM）更小，药物损失（DL）更高。各种乳糖等级的体外气溶胶化性能以下列沉积性能顺序排列：GRA>TAB>LAC≈CEL>FLO。建立了线性关系，表明为了将 SS 最大程度地输送到下呼吸道区域，更细长、更不规则形状和更粗糙的乳糖颗粒是优选的。因此，通过仔细选择包含在 DPI 制剂中的乳糖等级，可以显著提高 DPI 的性能。
