Santinho A J, Pereira N L, de Freitas O, Collett J H
Department of Pharmaceutical Sciences, University of Sao Paulo (FCFRP-USP), Av. do Café s/n, 14040-903, Ribeirão Preto, Brazil.
Int J Pharm. 1999 Sep 20;186(2):191-8. doi: 10.1016/s0378-5173(99)00171-4.
Casein microparticles (CAS/MP) have a potential clinical use for targeting drugs. However, the use of organic solvents in their preparation is undesirable. This study was designed to investigate the influence of preparation procedures in aqueous media on the formulation and physicochemical properties of CAS/MP. The first stage involved the influence of the coacervating agents (lactic acid, succinic anhydride, succinic acid and tartaric acid). The second stage studied was the influence of the ionic strength and the third, the influence of adding a thickener, hydroxypropyl cellulose or hydroxypropyl methycellulose (HPC or HPMC), and a plasticizing agent (gelatin). Some physicochemical properties of CAS/MP were evaluated. While the infrared and the thermal analysis showed that all coacervating agents were appropriate for coacervation, the scanning electron microscopy studies showed that the external morphology of the particles was more homogeneous when lactic acid was used. Utilizing lactic acid as the coacervating agent, there was a trend effect of adding NaCl implying that the increasing of the ionic strength resulted in better stability. Finally, the addition of 0.1% HPC plus either 0.25 or 0.5% gelatin resulted in homogeneous formulations. In conclusion, the use of lactic acid plus 0.1% HPC and 0.25% gelatin results in biodegradable and homogeneous CAS/MP, presenting a potentially useful drug delivery system.
酪蛋白微粒（CAS/MP）在药物靶向方面具有潜在的临床应用价值。然而，在其制备过程中使用有机溶剂是不可取的。本研究旨在探讨在水介质中制备工艺对CAS/MP制剂及其理化性质的影响。第一阶段涉及凝聚剂（乳酸、琥珀酸酐、琥珀酸和酒石酸）的影响。第二阶段研究的是离子强度的影响，第三阶段研究的是添加增稠剂羟丙基纤维素或羟丙基甲基纤维素（HPC或HPMC）以及增塑剂（明胶）的影响。对CAS/MP的一些理化性质进行了评估。虽然红外光谱和热分析表明所有凝聚剂都适合凝聚，但扫描电子显微镜研究表明，使用乳酸时颗粒的外部形态更均匀。以乳酸作为凝聚剂，添加氯化钠存在一种趋势效应，这意味着离子强度的增加会导致更好的稳定性。最后，添加0.1%的HPC加0.25%或0.5%的明胶可得到均匀的制剂。总之，使用乳酸加0.1%的HPC和0.25%的明胶可得到可生物降解且均匀的CAS/MP，呈现出一种潜在有用的药物递送系统。
