College of Pharmacy, University of Iowa, 115 S. Grand Avenue, Iowa City, IA 52242, USA.
Eur J Pharm Sci. 2013 Jan 23;48(1-2):142-52. doi: 10.1016/j.ejps.2012.10.004. Epub 2012 Oct 22.
Wet media milling by top down method has proved to be an effective method to prepare nanosuspension of poorly soluble drugs/APIs. Few or no attempts have been made so far to understand the feasibility of nanosuspension formulation in terms of the mechanism of stabilization as a function of drug properties. The objective of this study was to understand the effect of drug substance and stabilizer properties to form a successful nanosuspension product. From this study, logP and enthalpy were concluded to have a direct correlation on the feasibility of formation of a stable nanosuspension. The most likely candidate for media milling was a drug substance with a high enthalpy and hydrophobicity which can be stabilized either electrostatically or sterically. The least likely candidate will be one that is hydrophilic and having a very low enthalpy value. Also the choice of an ideal stabilizer/surfactant was found to be influenced by the degree of hydrophobicity of the drug itself. Finally the morphology of the starting drug was found to significantly affect the milling time required to produce submicron particles.
自上而下的湿法介质研磨已被证明是一种有效制备难溶性药物/API 纳米混悬剂的方法。迄今为止，几乎没有或没有尝试从稳定机制的角度来理解纳米混悬剂配方的可行性，这是药物性质的函数。本研究的目的是了解药物物质和稳定剂性质对形成成功的纳米混悬剂产品的影响。从这项研究中，可以得出结论，logP 和焓与形成稳定纳米混悬剂的可行性之间存在直接关系。最有可能成为介质研磨候选药物的是具有高热和疏水性的药物物质，可以通过静电或空间位阻来稳定。最不可能的候选药物是亲水性且焓值非常低的药物物质。此外，理想稳定剂/表面活性剂的选择也受到药物本身疏水性程度的影响。最后，发现起始药物的形态显著影响生产亚微米颗粒所需的研磨时间。
