Nikolakakis I, Aragon O B, Malamataris S
Pharmacy Department, University of Thessaloniki, Greece.
J Pharm Pharmacol. 1998 Jul;50(7):713-21. doi: 10.1111/j.2042-7158.1998.tb07131.x.
The purpose of this study was to compare some indicators of capsule-filling performance, as measured by tapped density under different conditions, and elucidate possible quantitative relationships between variation of capsule fill-weight (%CV) and gravitational and inter-particle forces (attractive or frictional) derived from measurements of particle size, true density, low compression and tensile strength. Five common pharmaceutical diluents (lactose, maize starch, talc, Emcocel and Avicel) were investigated and two capsule-filling methods (pouring powder and dosator nozzle) were employed. It was found that for the pouring-type method the appropriateness of Hausner's ratio (HR), Carr's compressibility index (CC%) and Kawakita's constant (alpha) as indicators of capsule fill-weight variation decreases in the order alpha > CC% > HR; the appropriateness of these indicators also decreases with increasing cylinder size and with impact velocity during tapping. For the dosator-type method the appropriateness of the indicators decreases in the order HR > CC% > alpha, the opposite of that for the pouring-type method; the appropriateness of the indicators increases with decreasing cylinder size and impact velocity. The relationship between %CV and the ratio of inter-particle attractive to gravitational forces calculated from measurements of particle size and true density (Fvdw/Wp) was more significant for the pouring-type capsule-filling method. For the dosator-type method a significant relationship (1% level) was found between %CV and the product of Fvdw/Wp and a function expressing the increase, with packing density (p(f)), in the ratio of frictional to attractive inter-particle forces derived from compression (P) and tensile-strength (T) testing, d(log(P/T))/d(p(f)). The value of tapped density in predictions of capsule-filling performance is affected by the testing conditions in a manner depending on the filling method applied. For the pouring-type method predictions can be based on the ratio of attractive (inter-particle) to gravitational forces, whereas for the dosator-type method the contribution of frictional and attractive forces should, because of packing density change, also be taken into account.
本研究的目的是比较在不同条件下通过振实密度测量的胶囊填充性能的一些指标，并阐明胶囊装量变化（%CV）与由粒度、真密度、低压缩强度和拉伸强度测量得出的重力和颗粒间力（吸引力或摩擦力）变化之间可能的定量关系。研究了五种常用的药用稀释剂（乳糖、玉米淀粉、滑石粉、羟丙基甲基纤维素和微晶纤维素），并采用了两种胶囊填充方法（粉末倾注法和定量给料喷嘴法）。结果发现，对于倾注式方法，豪斯纳比率（HR）、卡尔压缩性指数（CC%）和川北常数（α）作为胶囊装量变化指标的适用性按α > CC% > HR的顺序降低；这些指标的适用性也随着量筒尺寸的增加和振实过程中的冲击速度而降低。对于定量给料式方法，这些指标的适用性按HR > CC% > α的顺序降低，与倾注式方法相反；这些指标的适用性随着量筒尺寸和冲击速度的降低而增加。对于倾注式胶囊填充方法，%CV与根据粒度和真密度测量计算出的颗粒间吸引力与重力之比（Fvdw/Wp）之间的关系更为显著。对于定量给料式方法，在%CV与Fvdw/Wp的乘积以及一个表示随着堆积密度（p(f)）增加，由压缩（P）和拉伸强度（T）测试得出的颗粒间摩擦力与吸引力之比的函数d(log(P/T))/d(p(f))之间发现了显著关系（1%水平）。振实密度在胶囊填充性能预测中的值受测试条件的影响，其方式取决于所应用的填充方法。对于倾注式方法，预测可以基于吸引力（颗粒间）与重力之比，而对于定量给料式方法，由于堆积密度变化，摩擦力和吸引力的贡献也应予以考虑。
