Tunón Asa, Gråsjö Johan, Alderborn Göran
Department of Pharmacy, Uppsala University, Box 580, SE-751 23, Uppsala, Sweden.
Eur J Pharm Sci. 2003 Aug;19(5):333-44. doi: 10.1016/s0928-0987(03)00106-4.
In this study, reservoir pellets were prepared and their compression behaviour as well as the importance of their porosity for compression-induced changes in drug release was investigated. Pellets of three different porosities, consisting of microcrystalline cellulose and salicylic acid, were prepared by extrusion-spheronisation and spray-coated with ethyl cellulose (ethanol solution). Lubricated reservoir pellets were compressed and retrieved by deaggregation of the tablets. The retrieved pellets were analysed regarding porosity, thickness, surface area, shape and drug release. It was found that the coating did not significantly affect their compression behaviour. Compaction of pellets of high original porosity considerably affected densification and degree of deformation, whereas the effect on drug release was minor. For low porosity pellets the influence of compaction on drug release was appreciable, but only slight regarding densification and degree of deformation. In conclusion, the porosity of pellets is a potential factor that the formulator can use to optimize drug release and one that can affect the robustness of a formulation during manufacture. Moreover, the coating may be able to adapt to the densification and deformation of the pellets.
在本研究中，制备了储库型微丸，并研究了其压缩行为以及孔隙率对压缩诱导药物释放变化的重要性。由微晶纤维素和水杨酸组成的三种不同孔隙率的微丸通过挤出滚圆法制备，并用乙基纤维素（乙醇溶液）进行喷雾包衣。对润滑后的储库型微丸进行压缩，并通过片剂解聚回收微丸。对回收的微丸进行孔隙率、厚度、表面积、形状和药物释放分析。结果发现，包衣对其压缩行为没有显著影响。高初始孔隙率微丸的压实对致密化和变形程度有很大影响，而对药物释放的影响较小。对于低孔隙率微丸，压实对药物释放的影响明显，但对致密化和变形程度的影响较小。总之，微丸的孔隙率是制剂设计者可用于优化药物释放的一个潜在因素，也是一个在制造过程中会影响制剂稳健性的因素。此外，包衣可能能够适应微丸的致密化和变形。
