Drug Nanoparticles: Formulating Poorly Water-Soluble Compounds
Drug Nanoparticles: Formulating Poorly Water-Soluble Compounds
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DOI：
10.1177/0192623307310946
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发表时间：
2008-01-01
影响因子：
1.5
通讯作者：
Liversidge, Gary G.
中科院分区：
文献类型：
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作者：
Merisko-Liversidge, Elaine M.;Liversidge, Gary G.
通过组合筛选程序鉴定的化合物中有40%以上难溶于水。这些分子难以使用常规方法配制，并且与无数与配制相关的性能问题相关。将这些化合物配制成纯药物纳米颗粒是应用于这类分子的较新的药物递送策略之一。纳米颗粒分散体是稳定的并且具有小于1微米的平均直径。该制剂由水、药物和一种或多种通常被认为是安全的赋形剂组成。这些液体分散体表现出可接受的保质期，并且可以后加工成各种类型的固体剂型。药物纳米颗粒已被证明可以提高生物利用度，并增强口服和肠胃外剂型的药物暴露。用于最常用给药途径的合适制剂可以用毫克量的药物物质来鉴定，为发现科学家提供了筛选和鉴定上级类似物的替代途径。对于毒理学家，该方法提供了一种使用商业上可行的制剂进行剂量递增的方法。在过去的几年中，使用纳米颗粒方法配制水溶性差的化合物已经从概念发展到实现，其多功能性和适用性刚刚开始实现。
More than 40% of compounds identified through combinatorial screening programs are poorly soluble in water. These molecules are difficult to formulate using conventional approaches and are associated with innumerable formulation-related performance issues. Formulating these compounds as pure drug nanoparticles is one of the newer drug-delivery strategies applied to this class of molecules. Nanoparticle dispersions are stable and have a mean diameter of less than 1 micron. The formulations consist of water, drug, and one or more generally regarded as safe excipients. These liquid dispersions exhibit an acceptable shelf-life and can be postprocessed into various types of solid dosage forms. Drug nanoparticles have been shown to improve bioavailability and enhance drug exposure for oral and parenteral dosage forms. Suitable formulations for the most commonly used routes of administration can be identified with milligram quantities of drug substance, providing the discovery scientist with an alternate avenue for screening and identifying superior analogs. For the toxicologist, the approach provides a means for dose escalation using a formulation that is commercially viable. In the past few years, formulating poorly water-soluble compounds using a nanoparticulate approach has evolved from a conception to a realization whose versatility and applicability are just beginning to be realized.