INSERM 1008, College of Pharmacy, Univ. Lille Nord de France, 3 Rue du Prof. Laguesse, 59006 Lille, France.
Int J Pharm. 2012 Jan 17;422(1-2):75-82. doi: 10.1016/j.ijpharm.2011.10.030. Epub 2011 Oct 20.
Dry powder formulations are often composed of fine drug particles and coarser carrier particles, typically alpha-lactose monohydrate. However, the performance of a powder formulation may be highly dependent on the lactose quality and source. This study investigated the characteristics of lactose that influence the drug-to-carrier interaction and the performance of lactose-based dry powder inhaler formulations. The selected lactoses differed in the preparation processes and the content of fine lactose particles. Efficiency testing was done using fluticasone propionate and terbutaline sulphate as model drugs. Inverse gas chromatography was used to determine the surface heterogeneity distribution of different energy sites of the lactose and to understand the mechanism by which the fine carrier particles can improve the performance of dry powder inhalers. To assess the adhesion of respirable-sized drug to carrier particles, a simple method was developed based on aspiration and considering the whole blend as it is used in dry powder inhalers. When the percentage of fine lactose is high, a lower quantity of drug adheres to the lactose and/or the adhesion force is also lower. This was confirmed by the aerosolization assays done in the TSI (twin stage impinger). A correlation was observed between adhesion characteristics and inertial impaction. For both drugs, the fine particle fractions were highest in blends that present a greater proportion of lactose fine particles. A fairly good correlation between the fine particle fractions of both drugs and the peak max value and the AUC (area under curve) were found by inverse gas chromatography. With higher fine particle fraction values, which correspond to higher content of fines, the peak maxima determined by inverse gas chromatography were shifted to higher adsorption potentials, which supports the agglomeration hypothesis.
干粉制剂通常由细药物颗粒和较粗的载体颗粒组成，通常为α-乳糖一水合物。然而，粉末制剂的性能可能高度依赖于乳糖的质量和来源。本研究探讨了影响药物与载体相互作用和基于乳糖的干粉吸入剂制剂性能的乳糖特性。所选乳糖在制备工艺和细乳糖颗粒含量上存在差异。使用丙酸氟替卡松和硫酸特布他林作为模型药物进行效率测试。反气相色谱法用于确定乳糖不同能量位的表面不均匀分布，以了解细载体颗粒如何改善干粉吸入器的性能。为了评估可吸入大小的药物与载体颗粒的粘附性，开发了一种简单的方法，该方法基于抽吸，并考虑到干粉吸入器中使用的整个混合物。当细乳糖的百分比高时，与乳糖结合的药物量较少，或者粘附力也较低。这通过在 TSI（双级撞击器）中进行的雾化测定得到了证实。观察到粘附特性与惯性撞击之间存在相关性。对于两种药物，在具有较大比例乳糖细颗粒的混合物中，细颗粒分数最高。通过反气相色谱法发现，两种药物的细颗粒分数与峰最大值和 AUC（曲线下面积）之间存在相当好的相关性。随着细颗粒分数值的增加，即细颗粒含量的增加，反气相色谱法确定的峰最大值向更高的吸附势转移，这支持了团聚假说。
