School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore 637459, Singapore.
J Colloid Interface Sci. 2012 Feb 1;367(1):518-26. doi: 10.1016/j.jcis.2011.10.011. Epub 2011 Oct 18.
The dissolution rate and solubility of poorly soluble drugs can be enhanced by formulating them into stable amorphous nanoparticle complex (nanoplex). For this purpose, a highly sustainable self-assembly drug-polyelectrolyte complexation process is developed, with ciprofloxacin and dextran sulfate as the drug and polyelectrolyte models, respectively. The nanoplex are prepared by mixing two aqueous salt solutions - one containing the drug and the other containing the oppositely charged polyelectrolyte. The nanoplex suspension is transformed into stable dry-powder form by freeze-drying. The effects of drug concentration, drug-to-polyelectrolyte charge ratio, and salt concentration on the complexation efficiency, yield, drug loading, and nanoplex morphology are examined. The dissolution rates and solubility of the nanoplex are characterized and compared to raw drug crystals. Nearly spherical amorphous nanoplex having fairly uniform sizes in the range of 200-400 nm and 80% drug loading are successfully produced at ≥80% complexation efficiency and yield. The complexation efficiency is governed by the drug concentration and its ratio to the salt concentration. The nanoplex powders exhibit approximately twice higher dissolution rate and solubility than raw drug crystals and remain stable after one-month storage. Overall, amorphous nanoplex represent a promising bioavailability-enhanced formulation of poorly soluble drugs owed to their superior characteristics and ease of preparation.
通过将难溶性药物制成稳定的无定形纳米颗粒复合物（纳米复合物），可以提高其溶解速率和溶解度。为此，开发了一种高度可持续的自组装药物-聚电解质复合过程，以环丙沙星和葡聚糖硫酸盐分别作为药物和聚电解质模型。纳米复合物是通过将两种含有药物和带相反电荷的聚电解质的盐溶液混合制备的。将纳米复合物混悬液通过冷冻干燥转化为稳定的干粉形式。考察了药物浓度、药物-聚电解质电荷比和盐浓度对复合物效率、产率、载药量和纳米复合物形态的影响。对纳米复合物的溶解速率和溶解度进行了表征，并与原料药晶体进行了比较。在≥80%的复合物效率和产率下，成功制备了近球形无定形纳米复合物，粒径在 200-400nm 范围内，粒径较为均匀，载药量高达 80%。复合物效率受药物浓度及其与盐浓度的比值控制。纳米复合物粉末的溶解速率和溶解度比原料药晶体高约两倍，在储存一个月后仍保持稳定。总体而言，无定形纳米复合物因其优异的特性和易于制备而成为提高难溶性药物生物利用度的有前途的制剂。
