Abstract This study investigated comparative impact of different binder addition methods (pouring, dripping, spraying), binders and diluents on resulting granule and tablet attributes via high shear wet granulation. Lactose monohydrate and mannitol as diluents, and hydroxypropyl methylcellulose (HPMC E5) and polyvinylpyrrolidone (PVP K30) as binders were used. Granules were characterized for morphology, bulk-density, tapped-density, flow, size, segregation-potential and friability. To determine granule friability, procedure described in European Pharmacopoeia was slightly modified to reduce manual-variations and obtain appreciable discrimination between the formulations. Binder-diluent affinity was assessed by measuring contact angles of diluent-dispersion droplets on binder films over a period of time. All blends were pressed at the same compression force and resulting tablets were characterized for pharmacotechnical properties. Results revealed that the binder addition methods altered granule-shape, which predominantly governed the granule flow. The binder addition by spraying increased fines, blend segregation-potential, granule friability, tablet tensile-strength and tablet disintegration-time; binder addition by pouring showed an opposite impact. Mannitol granules exhibited lower bulk density, superior flow, lower segregation-potential and higher friability than their lactose counterparts. Amongst binders, PVP produced more friable granules compared to HPMC. The high polydispersity-index of polymer-binder induced non-homogeneity facilitating the blend segregation-potential. Due to higher affinity, HPMC was suitable binder for mannitol, and PVP for lactose to promote granule growth. The binder-diluent affinity dominated viscosity and surface tension of binder solution to improve granule size. Increase in granule size decreased granule-friability, which subsequently decreased tablet hardness, tensile-strength and disintegration-time. Mannitol produced harder tablets, and lactose tablets disintegrated faster by all binders and binder addition methods.

中文翻译：

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不同粘合剂添加方法、粘合剂和稀释剂对高剪切湿法制粒所得颗粒和片剂属性的比较影响

摘要 本研究通过高剪切湿法制粒，研究了不同粘合剂添加方法（浇注、滴注、喷雾）、粘合剂和稀释剂对所得颗粒和片剂属性的比较影响。使用乳糖一水合物和甘露醇作为稀释剂，并使用羟丙基甲基纤维素（HPMC E5）和聚乙烯吡咯烷酮（PVP K30）作为粘合剂。颗粒的特征在于形态、堆积密度、振实密度、流动性、尺寸、分离潜力和脆碎度。为了确定颗粒的脆性，欧洲药典中描述的程序稍作修改，以减少人工变化并获得配方之间的明显区分。通过测量一段时间内粘合剂薄膜上的稀释剂分散液滴的接触角来评估粘合剂-稀释剂的亲和力。以相同的压力压制所有混合物，并表征所得片剂的药物技术特性。结果表明，粘合剂添加方法改变了颗粒形状，这主要控制了颗粒流动。喷雾添加粘合剂增加了细粒、混合物的离析能力、颗粒脆碎度、片剂抗张强度和片剂崩解时间；通过浇注添加粘合剂显示出相反的影响。与乳糖对应物相比，甘露醇颗粒表现出更低的堆积密度、优异的流动性、更低的分离潜力和更高的脆性。在粘合剂中，与 HPMC 相比，PVP 产生的颗粒更易碎。聚合物粘合剂的高多分散指数导致非均匀性，促进了共混物的分离潜力。由于具有较高的亲和力，HPMC 是甘露醇的合适结合剂，乳糖的 PVP 促进颗粒生长。粘合剂-稀释剂亲和性支配粘合剂溶液的粘度和表面张力以改善颗粒尺寸。颗粒大小的增加降低了颗粒的脆碎度，从而降低了片剂硬度、拉伸强度和崩解时间。甘露醇生产出更硬的片剂，而所有粘合剂和粘合剂添加方法都会使乳糖片剂崩解得更快。