The increasing frequency at which poorly soluble new chemical entities are being discovered raises concerns in the pharmaceutical industry about drugability associated with erratic dissolution and low bioavailability of these hydrophobic compounds. Nanonization provides a plausible pharmaceutical basis for enhancing oral bioavailability and therapeutic effectiveness of these compounds by increasing their surface area. This paper surveys methods available to pharmaceutical manufacturing nanoparticles, including wet chemical processes, media milling, high pressure homogenization, gas-phase synthesis, and form-in-place processes, and elaborates physicochemical rational and gastrointestinal physiological basis upon which nano-drugs can be readily absorbed. Relevant examples are illustrated to show that nano-drugs permeate Caco-2 cell monolayer fast and are well absorbed into animal systemic circulation with high T(max) and AUC, resulting in oral bioavailability higher than their counterpart micro-drugs. The size-dependent permeability and bioavailability should be given particular consideration in the development of potent and selective drug candidates with poor aqueous solubility.

中文翻译：

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纳米颗粒配方提高难溶性药物的口服生物利用度：接近实验证据和理论。

发现难溶性新化学实体的频率越来越高，这引起了制药行业对与这些疏水性化合物的不稳定溶解和低生物利用度相关的可药性的担忧。纳米化为通过增加这些化合物的表面积来提高这些化合物的口服生物利用度和治疗效果提供了合理的药物基础。本文调查了可用于药物制造纳米颗粒的方法，包括湿化学工艺、介质研磨、高压均质、气相合成和就地成型工艺，并阐述了纳米药物可基于的理化合理和胃肠道生理基础。容易吸收。相关实例说明纳米药物可快速渗透Caco-2细胞单层，并能很好地吸收到动物体循环中，具有较高的T(max)和AUC，导致口服生物利用度高于其对应的微型药物。在开发具有较差水溶性的有效和选择性候选药物时，应特别考虑大小依赖的渗透性和生物利用度。