GEA-NUS Pharmaceutical Processing Research Laboratory, Department of Pharmacy and Pharmaceutical Sciences, National University of Singapore, 18 Science Drive 4, 117543, Singapore.
GEA-NUS Pharmaceutical Processing Research Laboratory, Department of Pharmacy and Pharmaceutical Sciences, National University of Singapore, 18 Science Drive 4, 117543, Singapore; Airlangga University, Kampus C Mulyorejo, Surabaya 60115, Indonesia.
Int J Pharm. 2024 Aug 15;661:124467. doi: 10.1016/j.ijpharm.2024.124467. Epub 2024 Jul 14.
Tablet disintegration is crucial for drug release and subsequent systemic absorption. Although factors affecting the disintegrant's functionality have been extensively studied, the impact of wet granulation on the performance of disintegrants in a poorly water-soluble matrix has received much less attention. In this study, the disintegrants, crospovidone (XPVP), croscarmellose sodium (CCS) and sodium starch glycolate (SSG), were wet-granulated with dibasic calcium phosphate dihydrate as the poorly water-soluble matrix and polyvinylpyrrolidone as the binder. The effect of wet granulation was studied by evaluating tablet tensile strength and disintegratability. Comparison between tablets with granulated or ungranulated disintegrants as well those without disintegrants were also made. Different formulations showed different degrees of sensitivity to changes in tablet tensile strength and disintegratability post-wet granulation. Tablet tensile strength decreased for tablets with granulated disintegrant XPVP or CCS, but to a smaller extent for SSG. While tablets with granulated XPVP or CCS had increased disintegration time, the increment was lesser than for SSG, suggesting that wet granulation impacted a swelling disintegrant more. The findings showed that tablets with wet-granulated disintegrant had altered the disintegrant's functionality. These findings could provide better insights into changes in the disintegrant's functionality after wet granulation.
片剂崩解是药物释放和随后全身吸收的关键。虽然影响崩解剂功能的因素已经得到了广泛的研究，但湿法制粒对崩解剂在难溶性基质中性能的影响却受到了较少的关注。在这项研究中，将崩解剂交联聚维酮（XPVP）、交联羧甲基纤维素钠（CCS）和交联羧甲基淀粉钠（SSG）与二水合磷酸氢钙作为难溶性基质和聚乙烯吡咯烷酮作为粘合剂进行湿法制粒。通过评估片剂的拉伸强度和崩解性来研究湿法制粒的效果。还比较了含有颗粒状或无颗粒状崩解剂以及不含崩解剂的片剂。不同的配方对湿法制粒后片剂拉伸强度和崩解性的变化表现出不同程度的敏感性。含有颗粒状崩解剂 XPVP 或 CCS 的片剂的拉伸强度降低，但 SSG 的降低程度较小。虽然含有颗粒状 XPVP 或 CCS 的片剂的崩解时间增加，但增加幅度小于 SSG，这表明湿法制粒对溶胀性崩解剂的影响更大。研究结果表明，含有湿法制粒崩解剂的片剂改变了崩解剂的功能。这些发现可以更好地了解湿法制粒后崩解剂功能的变化。
