Kocbek P, Baumgartner S, Kristl J
University of Ljubljana, Faculty of Pharmacy, Askerceva 7, 1000 Ljubljana, Slovenia.
Int J Pharm. 2006 Apr 7;312(1-2):179-86. doi: 10.1016/j.ijpharm.2006.01.008. Epub 2006 Feb 15.
Poorly water-soluble compounds are difficult to develop as drug products using conventional formulation techniques and are frequently abandoned early in discovery. In the present study, the melt emulsification method traditionally used to prepare solid lipid nanoparticles was adapted to produce drug nanosuspensions. The method was evaluated in comparison with the well known solvent diffusion process for ibuprofen as a model drug. Control of the preparation variables (stabilizers, drug content, homogenization procedure and cooling conditions) allowed formation of nanosuspensions with diameters less than 100 nm. The major advantage of the melt emulsification method over the solvent diffusion method is the avoidance of organic solvents during production, although the mean particle size is slightly greater. The combination of Tween 80 and PVP K25 as stabilizers yields nanosuspensions with the smallest average particle size. The formulation of ibuprofen as a nanosuspension, either in the form of lyophilized powder or granules, was very successful in enhancing dissolution rate, more than 65% of the drug being dissolved in the first 10 min compared to less than 15% of the micronized drug. The increase in in vitro dissolution rate may favourably affect bioavailability and improve safety for the patient by decreasing gastric irritancy.
水溶性差的化合物难以使用传统制剂技术开发成药品，并且在发现早期经常被放弃。在本研究中，传统上用于制备固体脂质纳米粒的熔融乳化法被用于制备药物纳米混悬液。以布洛芬作为模型药物，该方法与广为人知的溶剂扩散法进行了比较评估。通过控制制备变量（稳定剂、药物含量、均质化程序和冷却条件），可以形成直径小于100nm的纳米混悬液。与溶剂扩散法相比，熔融乳化法的主要优点是在生产过程中避免使用有机溶剂，尽管平均粒径略大。吐温80和聚乙烯吡咯烷酮K25作为稳定剂的组合可产生平均粒径最小的纳米混悬液。将布洛芬制成纳米混悬液，无论是冻干粉末还是颗粒形式，在提高溶出速率方面都非常成功，与微粉化药物不到15%相比，超过65%的药物在前10分钟内溶解。体外溶出速率的提高可能会对生物利用度产生有利影响，并通过降低胃部刺激性来提高患者的安全性。
