Hao Jianyuan, Whitaker Martin J, Wong Ben, Serhatkulu Gulay, Shakesheff Kevin M, Howdle Steven M
School of Chemistry, University of Nottingham, Nottingham, Tissue Engineering Group, UK NG7 2RD.
J Pharm Sci. 2004 Apr;93(4):1083-90. doi: 10.1002/jps.20002.
Exposure of poly(DL-lactic acid) (PDLLA), and related polymers, to supercritical CO2 (scCO2) at or below, physiological temperatures leads to very effective plasticization and liquefying of the polymers. The phenomenon arises from the high solubility and interaction of the scCO2 in the polymer. Under these unique conditions, temperature and solvent labile molecules can be mixed efficiently into the liquefied polymer. This liquefied polymer/drug/CO2 mixture can then be sprayed into a collecting chamber, and during this process particles of drug-loaded polymer are formed. This process is very different from rapid expansion and antisolvent based techniques that have been previously reported. In this article, we describe a method of controlling particle size during the spray process by introducing a backpressure of N2 in the collecting chamber. This backpressure dynamically regulates the loss of CO2 from the issuing polymer/CO2 mixture, leading to control over sprayed particle size. In situ observation of the viscosity of the plasticized polymer indicates that a backpressure of 68 bar or greater is necessary to ensure the production of fine particles. The influences of backpressure and saturation temperature on particle size for the sprayed products are discussed in terms of observed PDLLA/CO2 mixture viscosities.
聚（DL-乳酸）（PDLLA）及相关聚合物在生理温度及以下暴露于超临界二氧化碳（scCO2）会导致聚合物非常有效地增塑和液化。这种现象源于scCO2在聚合物中的高溶解度和相互作用。在这些独特条件下，对温度和溶剂敏感的分子能够高效地混入液化的聚合物中。然后可以将这种液化的聚合物/药物/二氧化碳混合物喷入收集腔室，在此过程中形成载药聚合物颗粒。这个过程与先前报道的基于快速膨胀和抗溶剂的技术有很大不同。在本文中，我们描述了一种通过在收集腔室中引入氮气背压来控制喷雾过程中颗粒大小的方法。这种背压动态调节从喷出的聚合物/二氧化碳混合物中二氧化碳的损失，从而控制喷雾颗粒的大小。对增塑聚合物粘度的原位观察表明，需要68巴或更高的背压才能确保产生细颗粒。根据观察到的PDLLA/二氧化碳混合物粘度，讨论了背压和饱和温度对喷雾产品颗粒大小的影响。
