Department of Pharmaceutical Engineering, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
Int J Pharm. 2013 May 1;448(1):1-8. doi: 10.1016/j.ijpharm.2013.03.012. Epub 2013 Mar 19.
With the aim of directly predicting the functionality and mechanism of disintegrants during the disintegration and dissolution of tablets, we investigated an analysis method based on available surface area, which is the surface area of a drug in a formulation in direct contact with the external solvent during dissolution. We evaluated the following disintegrants in this study: sodium starch glycolate (Glycolys), crospovidone (Kollidon CL), carboxymethylcellulose calcium (CMC-Ca), low-substituted hydroxypropylcellulose (L-HPC), and croscarmellose sodium (Ac-Di-Sol). When disintegrant was added to a 50% ethenzamide tablet formulation, an increase in the dissolution rate dependent on disintegrant concentration was observed, according to the type of disintegrant. In addition, the available surface area also differed between disintegrants. For Glycolys, CMC-Ca, and Ac-Di-Sol, a rapid increase in available surface area and a large increase in maximum available surface area (Smax) were observed due to high swellability and wicking, even when the disintegrant concentration was only 1.0%. In contrast, for Kollidon CL and LH-21, a gradual increase in available surface area was observed, depending on the disintegrant concentration. To evaluate the disintegrant ability, Δtmax and ΔSmax were calculated by subtracting peak time (tmax) at 5.0% from that at 1.0% and subtracting Smax at 1.0% from that at 5.0%, respectively, and it was found that the water absorption ratio had strong negative correlations with Δtmax and ΔSmax. Therefore, this study demonstrates that analysis of only available surface area and parameters thereby obtained can directly provide useful information, especially about the disintegration ability of disintegrants.
为了直接预测崩解剂在片剂崩解和溶解过程中的功能和机制，我们研究了一种基于可用表面积的分析方法，该方法是药物在溶解过程中与外部溶剂直接接触的制剂中的表面积。在这项研究中，我们评估了以下崩解剂：交联羧甲淀粉钠（Glycolys）、交联聚维酮（Kollidon CL）、羧甲基纤维素钙（CMC-Ca）、低取代羟丙基纤维素（L-HPC）和交联羧甲基纤维素钠（Ac-Di-Sol）。当崩解剂添加到 50%乙酰胺片剂配方中时，根据崩解剂的类型，观察到溶解速率随崩解剂浓度的增加而增加。此外，可用表面积在崩解剂之间也有所不同。对于 Glycolys、CMC-Ca 和 Ac-Di-Sol，由于高溶胀性和虹吸作用，即使崩解剂浓度仅为 1.0%，也观察到可用表面积的快速增加和最大可用表面积（Smax）的大幅增加。相比之下，对于 Kollidon CL 和 LH-21，观察到可用表面积随崩解剂浓度的逐渐增加。为了评估崩解剂能力，通过从 5.0%时的峰值时间（tmax）中减去 1.0%时的峰值时间（tmax）并从 1.0%时的 Smax 中减去 5.0%时的 Smax，分别计算了 Δtmax 和 ΔSmax，并发现吸水率与 Δtmax 和 ΔSmax 呈强负相关。因此，本研究表明，仅分析可用表面积及其获得的参数可以直接提供有用的信息，特别是关于崩解剂的崩解能力。
