Kushner Joseph, Schlack Holger
Drug Product Design, Pfizer Worldwide Research and Development, Eastern Point Road, MS 8156-033, Groton, CT 06340, USA.
Pfizer Global Supply, Freiburg, Germany.
Int J Pharm. 2014 Nov 20;475(1-2):147-55. doi: 10.1016/j.ijpharm.2014.08.036. Epub 2014 Aug 23.
An experimental study was conducted to verify that lubrication mixing in commercial-scale bin blenders can be described by a previously-reported lubrication blending process scale-up model. Specifically, the mixing of two placebo formulations (2:1 MCC:lactose, and 2:1 MCC:DCP) with 1% magnesium stearate in 100, 400, and 2000 L bin blenders at 30% and 70% blend fill levels for several extents of lubricant mixing was examined. The lubricated powder blends were assessed for bulk/tapped density and powder flow, as measured by Hausner's ratio. The blends were then compressed into tablets and evaluated for tensile strength, friability, and disintegration. It was observed that the lubrication rate constant, γ, for tablet tensile strength and for bulk specific volume were similar. Furthermore, powder flow, as measured by Hausner's ratio, improved with increased extent of lubrication. Tablet disintegration and tablet friability were both minimally affected as a result of extended lubrication for the placebos blends evaluated in this study. The results of this study confirm that the lubrication mixing model can be applied to scale-up the lubrication blending process from batches made in 30 mL bottle blenders to batches made in 2000 L bin blenders, which is a range of nearly five orders of magnitude.
进行了一项实验研究，以验证商业规模的料仓混合器中的润滑混合是否可以用先前报道的润滑混合过程放大模型来描述。具体而言，研究了在100升、400升和2000升的料仓混合器中，在30%和70%的混合填充水平下，两种安慰剂配方（2:1微晶纤维素:乳糖和2:1微晶纤维素:磷酸氢钙）与1%硬脂酸镁在几种润滑剂混合程度下的混合情况。对润滑后的粉末混合物进行了堆积密度/振实密度和粉末流动性评估，通过豪斯纳比率来衡量。然后将混合物压制成片剂，并评估其拉伸强度、脆碎度和崩解度。观察到片剂拉伸强度和堆积比容的润滑速率常数γ相似。此外，通过豪斯纳比率测量的粉末流动性随着润滑程度的增加而提高。在本研究中评估的安慰剂混合物中，延长润滑对片剂崩解和片剂脆碎度的影响都很小。这项研究的结果证实，润滑混合模型可用于将润滑混合过程从30毫升瓶式混合器中的批次放大到2000升料仓混合器中的批次，这一范围接近五个数量级。
