The effect of carrier surface treatment on drug particle detachment from crystalline carriers in adhesive mixtures for inhalation
The effect of carrier surface treatment on drug particle detachment from crystalline carriers in adhesive mixtures for inhalation
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DOI：
10.1016/j.ijpharm.2006.07.017
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发表时间：
2006-12-11
影响因子：
5.8
通讯作者：
Frijlink, H. W.
中科院分区：
文献类型：
--
作者：
Dickhoff, B. H. J.;de Boer, A. H.;Frijlink, H. W.
在这项研究中，乳糖载体表面处理的药物颗粒在吸入过程中脱离的影响进行了研究。市售α乳糖一水合物品牌的晶体通常表现出一定的表面粗糙度，并且在其表面上含有天然细粒和杂质，这些细粒和杂质影响吸入用粘合剂混合物中药物与载体的相互作用。浸没处理可以改变这些表面特性。将两种不同的筛分级分（63-90和250-355 μ m）浸没在乙醇和水的混合物（分别为96和80%v/v）中。显微镜观察和激光衍射分析表明，无论是形状还是尺寸的载体颗粒被浸没处理改变。然而，比表面积和杂质的量似乎大大减少后，浸没，和减少的幅度是不同的乙醇-水的混合物。比表面积的减少特别归因于从载体表面除去粘附的乳糖细粉。在治疗前后制备与布地奈德的混合物（在广泛的载体有效载荷中）。从各种混合物中的药物颗粒分离进行了研究与筛分试验，并在30和601/min的级联冲击器分析。使用两种不同类型的吸入器，一个产生升力和阻力（ISF吸入器）和一个产生惯性力（测试吸入器），分别。级联冲击器和筛测试实验表明，载体表面光滑度的增加导致吸入过程中药物颗粒脱离减少，这与所使用的吸入器类型无关。这种减少可归因于粘附的乳糖细粉的去除，其可为药物颗粒提供在混合期间免受压力的遮蔽。(c)2006 Elsevier B. V.保留所有权利。
In this study, the effect of lactose carrier surface treatment on drug particle detachment during inhalation has been investigated. Crystals of marketed brands of alpha lactose monohydrate brands normally exhibit a certain surface rugosity and contain natural fines and impurities on their surface, which influence the drug-to-carrier interaction in adhesive mixtures for inhalation. Submersion treatment may change these surface characteristics. Two different sieve fractions (63-90 and 250-355 mu m) were submerged in mixtures of ethanol and water (96 and 80% v/v, respectively). Microscopic observation and laser diffraction analysis revealed that neither the shape nor the size of the carrier particles was changed by the submersion treatment. However, the specific surface area and the amount of impurities appeared to decrease substantially after submersion, and the magnitude of the decrease was different for the different ethanol-water mixtures. The reduction in specific surface area was attributed particularly to the removal of the adhering lactose fines from the carrier surface. Mixtures with budesonide (in a wide range of carrier payloads) were prepared before and after treatment. Drug particle detachment from the various mixtures was studied with a sieve test and with a cascade impactor analysis at 30 and 601/min. Two different types of inhalers were used, one generating lift- and drag-forces (ISF inhaler) and one generating inertial forces (test inhaler), respectively. The cascade impactor and sieve test experiments showed that an increase in carrier surface smoothness results in a reduced drug particle detachment during inhalation, which was independent of the type of inhaler used. This reduction could be attributed to the removal of the adhering lactose fines which may provide shelter for the drug particles from press-on forces during mixing. (c) 2006 Elsevier B.V. All rights reserved.