Osei-Yeboah Frederick, Zhang Minglun, Feng Yushi, Sun Changquan Calvin
Pharmaceutical Materials Science and Engineering Laboratory, Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, 55455.
J Pharm Sci. 2014 Aug;103(8):2434-40. doi: 10.1002/jps.24066. Epub 2014 Jul 1.
Granules prepared by the high shear wet granulation (HSWG) process commonly exhibit the problem of overgranulation, a phenomenon characterized by a severe loss of the ability to form adequately strong tablet. We hypothesize that the incorporation of brittle excipients promotes brittle fracture of granules during compaction, thereby improving tablet mechanical strength by increasing bonding area. On this basis, we have examined the effectiveness of incorporating a brittle excipient into a plastic matrix in addressing the overgranulation problem. A complete loss of tabletability is observed for plastic microcrystalline cellulose (MCC) when ≥ 55% of granulating water was used. The incorporation of a brittle excipient, either lactose or dibasic calcium phosphate (Dical) into the MCC matrix leads to improved tabletability in a concentration-dependent manner, with higher amount of brittle excipient being more effective. For each mixture, tablet tensile strength goes through a minimum as the granulating water increases, for example, 1.4 MPa for the mixture containing 80% of lactose and 2.1 MPa for the mixture containing 80% Dical. These results, along with scanning electron microscope evidence, show that the addition of brittle excipients to an otherwise plastic powder is an effective formulation strategy to address the overgranulation problem in HSWG.
通过高剪切湿法制粒（HSWG）工艺制备的颗粒通常存在过度制粒问题，这一现象的特征是形成足够强度片剂的能力严重丧失。我们推测，加入脆性辅料可促进颗粒在压片过程中的脆性断裂，从而通过增加结合面积提高片剂的机械强度。在此基础上，我们研究了在塑性基质中加入脆性辅料解决过度制粒问题的有效性。当使用≥55%的制粒水时，塑性微晶纤维素（MCC）的可压性完全丧失。在MCC基质中加入脆性辅料乳糖或磷酸氢钙（磷酸二钙），可使可压性呈浓度依赖性提高，脆性辅料用量越高效果越好。对于每种混合物，随着制粒水增加，片剂抗张强度会经历一个最小值，例如，含80%乳糖的混合物为1.4MPa，含80%磷酸氢钙的混合物为2.1MPa。这些结果以及扫描电子显微镜证据表明，在原本塑性的粉末中加入脆性辅料是解决HSWG中过度制粒问题的有效制剂策略。
