Phares AG, Muttenz, Switzerland.
Expert Opin Drug Deliv. 2011 Nov;8(11):1481-500. doi: 10.1517/17425247.2011.614228. Epub 2011 Sep 6.
For poorly soluble compounds, a good bioavailability is typically needed to assess the therapeutic index and the suitability of the compound for technical development. In industry, the selection of the delivery technology is not only driven by technical targets, but also by constraints, such as production costs, time required for development and the intellectual property situation.
This review covers current developments in parenteral and oral delivery technologies and products for poorly water-soluble compounds, such as nano-suspensions, solid dispersions and liposomes. In addition, the use of biorelevant dissolution media to assess dissolution and solubility properties is described. Suggestions are also included to systematically address development hurdles typical of poorly water-soluble compounds intended for parenteral or oral administration.
A holistic assessment is recommended to select the appropriate delivery technology by taking into account technical as well as intellectual property considerations. Therefore, first and foremost, a comprehensive physico-chemical characterization of poorly water-soluble compounds can provide the key for a successful selection and development outcome. In this context, the identified physical form of the compound in the formulation is used as a guide for a risk-benefit assessment of the selected oral delivery technology. The potential of nano-suspensions for intravenous administration is unclear. In the case of oral administration, nano-suspensions are mainly used to improve the oral absorption characteristics of micronized formulations. The development of an in situ instantaneous solubilization method, based on stable, standardized liposomes with low toxicity, opens new avenues to solubilize poorly water-soluble compounds.
对于难溶性化合物，通常需要良好的生物利用度来评估治疗指数和化合物是否适合技术开发。在工业界，输送技术的选择不仅受技术目标的驱动，还受生产成本、开发所需时间和知识产权状况等限制的影响。
本文综述了难溶性化合物（如纳米混悬剂、固体分散体和脂质体）的肠外和口服给药技术和产品的最新进展。此外，还描述了使用生物相关溶解介质评估溶解和溶解度性质。还提出了建议，以系统地解决用于肠外或口服给药的典型难溶性化合物的开发障碍。
建议通过考虑技术和知识产权因素，进行全面的评估来选择合适的输送技术。因此，首先，对难溶性化合物进行全面的物理化学特性分析，可以为成功的选择和开发结果提供关键信息。在这方面，制剂中化合物的确定物理形式可作为所选口服输送技术的风险-收益评估的指南。静脉内给药纳米混悬剂的潜力尚不清楚。对于口服给药，纳米混悬剂主要用于改善微粉化制剂的口服吸收特性。基于稳定、标准化、低毒性的脂质体的瞬时原位增溶方法的开发为增溶难溶性化合物开辟了新途径。
