Grasmeijer Floris, Grasmeijer Niels, Hagedoorn Paul, Frijlink Henderik Willem, Haaije de Boer Anne
University of Groningen, Department of Pharmaceutical Technology and Biopharmacy, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands.
Curr Pharm Des. 2015;21(40):5900-14. doi: 10.2174/1381612821666151008124622.
Adhesive mixtures for inhalation are the most widely used type of formulation in dry powder inhalation products. Although they have been the subject of active research, the relationships between properties of the starting materials, the mixing and dispersion processes, and the dispersion performance of this type of formulation are generally poorly understood. Interactions between relevant variables have been mentioned as an important cause. By reviewing the effects on mixture dispersion performance of the most widely studied formulation variables we try to find out whether or not the understanding of adhesive mixtures has improved in recent years. We furthermore propose an approach that may potentially accelerate the process of understanding. General conclusions concerning the effects of the variables considered cannot be drawn, because inconsistent findings are reported throughout the literature for all of them. These inconsistencies are indeed largely the result of interactions between variables of the formulation and dispersion processes. Mechanisms for most of the observed effects and interactions have been proposed, but they often remain unproven and, therefore, speculative. We have attempted to condense the knowledge from the literature into a theoretical framework that is intended to help explain the interplay between variables. According to this framework, only few mixture properties are key to understanding the effects of and interactions between formulation variables. Therefore, we suggest that the development or optimisation of techniques to accurately characterise these mixture properties could be an effective approach to further the fundamental understanding of adhesive mixtures for inhalation and enable their rational engineering.
吸入用粘合剂混合物是干粉吸入产品中使用最广泛的剂型。尽管它们一直是积极研究的对象，但对于这类制剂起始材料的性质、混合与分散过程以及分散性能之间的关系，人们普遍了解甚少。相关变量之间的相互作用被认为是一个重要原因。通过回顾研究最为广泛的制剂变量对混合物分散性能的影响，我们试图弄清楚近年来对粘合剂混合物的理解是否有所提高。此外，我们提出了一种可能会加速理解过程的方法。由于文献中针对所有这些变量都报道了不一致的结果，因此无法得出关于所考虑变量影响的一般性结论。这些不一致实际上很大程度上是制剂和分散过程变量之间相互作用的结果。对于大多数观察到的效应和相互作用的机制已经有人提出，但往往未经证实，因此具有推测性。我们试图将文献中的知识浓缩成一个理论框架，旨在帮助解释变量之间的相互作用。根据这个框架，只有少数混合物性质是理解制剂变量的影响及其相互作用的关键。因此，我们建议开发或优化准确表征这些混合物性质的技术，可能是进一步从根本上理解吸入用粘合剂混合物并实现其合理设计的有效方法。
