An easy-to-use approach for determining the disintegration ability of disintegrants by analysis of available surface area

• Published in: International journal of pharmaceutics 2013-05, Vol.448 (1), p.1-8
• Main Authors: Iwao, Yasunori, Tanaka, Shoko, Uchimoto, Takeaki, Noguchi, Shuji, Itai, Shigeru
• Format: Article
• Language: English
• Subjects: Absorption; Available surface area; calcium; carboxymethylcellulose; Carboxymethylcellulose Sodium - chemistry; Cellulose - analogs & derivatives; Cellulose - chemistry; direct contact; Disintegrant; Disintegration mechanism; drug formulations; Excipients - chemistry; Povidone - chemistry; prediction; Salicylamides - chemistry; sodium; Solubility; solvents; starch; Starch - analogs & derivatives; Starch - chemistry; surface area; Surface Properties; Tablets; Water - chemistry
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2013.03.012

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.