Sallam E, Ibrahim H, Dahab R A, Shubair M, Khalil E
R & D Division, Arab Pharmaceutical Manufacturing Co., Sult, Jordan.
Drug Dev Ind Pharm. 1998 Jun;24(6):501-7. doi: 10.3109/03639049809085650.
Effects of four fast disintegrants on the dissolution of terfenadine tablets containing the gas-evolving disintegrant, CaCO3, were evaluated. In addition, effects of presence of starch along with the fast disintegrants on the dissolution of the tablets were examined. Dissolution data were treated to give dissolution parameters which reflected efficiency of the disintegrant combinations. The four fast disintegrants improved disintegration/dissolution of the original formulation. The relative efficiency of improvement was in the order crospovidone > Ac-Di-Sol > Primojel > low substituted hydroxypropylcellulose. The presence of starch advertently affected the role of the fast disintegrants. Scanning electron microscope studies revealed that starch covered the drug-containing granules and other particles of the tablet. pH changes during dissolution of representative tablets in 0.1 N HCl solutions were determined at specific time intervals. The progressive decrease in rates of acid consumption as a function of the amount of starch, along with the SEM studies, suggested that a barrier existed around the tablet particles. The barrier was generated by the swelled starch grains and was responsible for the loss of the dissolution-improving capacity of the fast disintegrants. Furthermore, the barrier interfered with the diffusion of the hydronium ions and therefore, impaired the function of the disintegrant combination.
评估了四种快速崩解剂对含有产气崩解剂碳酸钙的特非那定片溶出度的影响。此外，还研究了淀粉与快速崩解剂共同存在时对片剂溶出度的影响。对溶出数据进行处理以得到反映崩解剂组合效率的溶出参数。四种快速崩解剂均改善了原制剂的崩解/溶出。改善的相对效率顺序为交联聚维酮＞乙酰化二淀粉磷酸酯＞预胶化淀粉＞低取代羟丙基纤维素。淀粉的存在显著影响了快速崩解剂的作用。扫描电子显微镜研究表明，淀粉覆盖了片剂中含药颗粒和其他颗粒。在特定时间间隔测定了代表性片剂在0.1 N盐酸溶液中溶出时的pH变化。随着淀粉量的增加，酸消耗速率逐渐降低，结合扫描电子显微镜研究表明，片剂颗粒周围存在屏障。该屏障由膨胀的淀粉颗粒形成，导致快速崩解剂溶出改善能力丧失。此外，该屏障干扰了水合氢离子的扩散，因此损害了崩解剂组合的功能。
