Theophylline formulation by supercritical antisolvents.
Theophylline formulation by supercritical antisolvents.
复制标题
采用超临界反溶剂配制茶碱。
DOI：
10.1016/j.ijpharm.2007.05.008
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发表时间：
2007
影响因子：
5.8
通讯作者：
P. Subra
中科院分区：
文献类型：
--
作者：
C. Roy;A. Vega;P. Subra
超临界抗溶剂沉淀已被用于生产茶碱颗粒作为纯晶体或作为与聚乳酸（PLA）的固体制剂。实验以间歇或半连续方法进行，并使用二氧化碳（CO2）或三氟甲烷（CHF 3）作为抗溶剂。两种模式都导致微粉化茶碱，但半连续产生比批次更小的颗粒。颗粒形态对反溶剂敏感，因为CO2-和CHF 3-样品分别呈现六边形和三角形形状。CO2粉末的最显著特征是茶碱表现出与粗品或CHF 3材料不同的晶格，这是由XRD图案中的新衍射峰认可的，而不是由样品的水合作用引起的。然而，无论是形状还是新的晶格影响茶碱的溶解动力学。对于与PLA的共沉淀，粉末的成功回收仅发生在CHF 3-分批和CO2-半连续的条件下。粉末保留了相应的纯加工茶碱的形状和结晶度，表明PLA不干扰药物的沉淀行为。此外，只有CO2-半连续产品表现出药物的释放速率降低和总释放时间延长。
Supercritical antisolvent precipitation has been used to produce theophylline particles as pure crystals or as a solid formulation with poly lactic acid (PLA). Experiments were carried out as batch or semi-continuous process and with carbon dioxide (CO2) or trifluoromethane (CHF3) as antisolvent. Both modes led to micronized theophylline, but the semi-continuous produced smaller particles than the batch. The particle morphology was sensitive to the antisolvent, since CO2- and CHF3-samples exhibited hexagonal and triangular shape, respectively. The most distinguish feature of CO2-powders was that theophylline exhibited a different crystal lattice than the crude- or the CHF3-materials, accredited by new diffraction peaks in the XRD patterns not attributable to hydration of samples. However, neither the shape nor the new crystal lattice influenced the dissolution kinetics of Theophylline. For co-precipitation with PLA, the successful recovery of a powder occurred only in conditions of CHF3-batch and CO2-semi continuous. The powder retained the shape and the crystallinity of the corresponding pure processed theophylline, indicating that PLA did not interfere with the precipitation behavior of the drug. Moreover, only the CO2-semi continuous products exhibited a decreased release rate and a prolongation of the total release time of the drug.