Krausbauer Etienne, Puchkov Maxim, Betz Gabriele, Leuenberger Hans
Institute of Pharmaceutical Technology, Pharmacenter, University of Basel, Klingelbergstrasse 50, Basel, Switzerland.
J Pharm Sci. 2008 Jan;97(1):529-41. doi: 10.1002/jps.21163.
The purpose of this study was to propose a method of determining the exact value of disintegrant ratio in a binary drug-disintegrant compacted mixture for a minimum disintegration time in the case of spherical particles. Disintegration is a limiting factor in dissolution process of compact for low water soluble active ingredients. As disintegration time is shortest at a certain ratio of disintegrant, a calculation of this value is important for solid dosage from design to enhance disintegration and dissolution process. According to percolation theory, a minimum disintegration time corresponds to the formation of a continuous water-conducting cluster through the entire tablet. The critical volumetric ratio at which the cluster is formed is named percolation threshold and has the value of 0.16 for random close packed (RCP) sphere systems. RCP systems where chosen as the best model for compacts consisting of spherical particles. Two cases for water diffusion through the tablet were identified, according to geometrical considerations between disintegrant and drug particles. These cases determine if disintegrant particles can have a contact between each other within the compact and thus if porosity and disintegrant volume are included in the continuous cluster. An equation for both cases is presented in the form of piecewise function to determine the minimal disintegrant volumetric ratio for a binary drug/disintegrant compact in order to achieve a minimum disintegration time. Disintegration tests were performed with tablets at different ratios of modified corn starch mixed with caffeine or paracetamol powders. Estimated and experimental optimal ratio were compared showing coefficient R(2) = 0.96.
本研究的目的是提出一种方法，用于确定二元药物-崩解剂压实混合物中崩解剂比例的精确值，以实现球形颗粒情况下的最短崩解时间。对于低水溶性活性成分，崩解是片剂溶出过程中的一个限制因素。由于在特定崩解剂比例下崩解时间最短，计算该值对于固体剂型设计以增强崩解和溶出过程很重要。根据渗流理论，最短崩解时间对应于贯穿整个片剂形成连续的导水簇。形成该簇的临界体积比称为渗流阈值，对于随机密堆积（RCP）球体系统，其值为0.16。RCP系统被选为球形颗粒组成的片剂的最佳模型。根据崩解剂和药物颗粒之间的几何关系，确定了水通过片剂扩散的两种情况。这些情况决定了崩解剂颗粒在片剂内是否能相互接触，从而决定孔隙率和崩解剂体积是否包含在连续簇中。以分段函数的形式给出了两种情况的方程，以确定二元药物/崩解剂片剂达到最短崩解时间所需的最小崩解剂体积比。用含有不同比例改性玉米淀粉与咖啡因或扑热息痛粉末混合的片剂进行了崩解试验。比较了估计的和实验得到的最佳比例，显示相关系数R(2)=0.96。
