Laboratory of Pharmaceutical Technology, Department of Pharmaceutics, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium.
Institute of Pharmaceutics and Biopharmaceutics, Heinrich-Heine-University, Universitätsstraße 1, 40225 Duesseldorf, Germany; Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands.
Int J Pharm. 2022 Aug 25;624:122012. doi: 10.1016/j.ijpharm.2022.122012. Epub 2022 Jul 14.
Internal lubrication with magnesium stearate (MgSt) is associated with a reduced tensile strength and prolonged disintegration and dissolution times. In the current study, alternative lubricants to MgSt were compared with regard to lubrication efficacy and their impact on tablet properties. The lubricants were combined in different concentrations (0.5-5% w/w) with three fillers (lactose, mannitol and microcrystalline cellulose (MCC)). The high lubrication efficiency of MgSt was associated with the highest reduction of tensile strength. The micronized stearic acid (SA) grades proved good alternatives as they showed a good lubrication efficiency in combination with a limited negative effect on tensile strength. The hydrophobic lubricants (e.g., MgSt and SA) did not prolong disintegration. In contrast, delayed disintegration was observed for sucrose monopalmitate combined with all three fillers and for several other hydrophilic lubricants (sodium lauryl sulfate, poloxamers 188 and P407) combined with MCC. These unexpected findings were explained by the competition-for-water hypothesis. The potential of alternative lubricants to MgSt was demonstrated in this study. Nevertheless, the impact of lubricant addition on process and tablet quality depended on lubricant (type and concentration) and formulation (lubrication need, deformation mechanism and disintegration behavior) properties. Therefore, lubricant selection should be carefully considered in formulation development.
硬脂酸镁（MgSt）的内润滑作用与拉伸强度降低和崩解及溶解时间延长有关。在本研究中，比较了替代 MgSt 的润滑剂在润滑效果及其对片剂性质的影响方面的情况。这些润滑剂分别与三种赋形剂（乳糖、甘露醇和微晶纤维素（MCC））以不同浓度（0.5-5%w/w）组合。MgSt 的高润滑效率与拉伸强度的最大降低有关。经微粉化的硬脂酸（SA）级是很好的替代品，因为它们在与拉伸强度的有限负面影响结合时显示出良好的润滑效率。疏水性润滑剂（如 MgSt 和 SA）不会延长崩解。相比之下，当与所有三种赋形剂组合时，单棕榈酸蔗糖酯和其他几种亲水性润滑剂（月桂基硫酸钠、泊洛沙姆 188 和 P407）与 MCC 组合时，观察到崩解延迟。这些意外发现可以用竞争水分假说来解释。本研究证明了替代 MgSt 的润滑剂的潜力。然而，润滑剂添加对工艺和片剂质量的影响取决于润滑剂（类型和浓度）和配方（润滑需求、变形机制和崩解行为）特性。因此，在制剂开发中应仔细考虑润滑剂的选择。
