Drug Product Development, AbbVie Inc., 1 N. Waukegan Road, North Chicago, Illinois 60064.
J Pharm Sci. 2019 Dec;108(12):3803-3813. doi: 10.1016/j.xphs.2019.08.019. Epub 2019 Aug 29.
The effect of particle surface area and adhesion force on sticking behavior for a model pharmaceutical blend was studied. Various lots of an active pharmaceutical ingredient (API) differing in particle size distribution and surface area were blended with commercial grades of microcrystalline cellulose ranging in size from 20 to 110 μm. A dry-coating technique was also used to modify the surface of microcrystalline cellulose to reduce its adhesion force. This allowed study of sticking behavior due to effects associated with particle adhesion force independently from effects associated with surface area. Using a removable-tip experiment to quantify the mass of adhered material to a tablet punch, this study concludes that both particle surface area and adhesion force significantly affect sticking behavior. Tablets with higher tensile strength comprised of API with lower surface area relative to the excipient surface area resulted in less sticking. This study found that the difference between the tablet tensile strength of the blend and that of the API normalized by the surface area fraction of API in the blend correlates well with the rate of mass adhered to the punch. This quantity, referred to as the sticking index, can be used to assess sticking propensity for a pharmaceutical blend.
研究了颗粒表面积和粘附力对模型药物混合物粘附行为的影响。将具有不同粒径分布和表面积的各种原料药(API)与粒径为 20 至 110 μm 的商用级微晶纤维素进行混合。还使用干法涂层技术来修饰微晶纤维素的表面,以降低其粘附力。这使得可以研究由于与颗粒粘附力相关的效应而引起的粘附行为,而与表面积相关的效应则独立于表面积相关的效应。通过使用可移除尖端实验来量化粘附到片剂冲头的材料的质量,本研究得出结论,颗粒表面积和粘附力都会显著影响粘附行为。由与辅料相比表面积更小的 API 组成的具有较高拉伸强度的片剂导致粘附性降低。本研究发现,混合物的片剂拉伸强度与通过混合物中 API 的表面积分数归一化的 API 的片剂拉伸强度之间的差异与粘附到冲头的质量增加率很好地相关。该量,称为粘附指数,可以用于评估药物混合物的粘附倾向。