Jamzad Shahla, Tutunji Lara, Fassihi Reza
Department of Pharmaceutical Sciences, School of Pharmacy, Temple University, 3307 N. Broad Street, Philadelphia, PA 19140, USA.
Int J Pharm. 2005 Mar 23;292(1-2):75-85. doi: 10.1016/j.ijpharm.2004.11.011.
The influence of water-soluble and insoluble excipients on dynamics of hydration, front movement, erosion, and drug release from hydrophilic matrix tablets containing water-soluble drug was studied. Tablets were manufactured by direct compression, and their un-constrained swelling behavior and gel strength were assessed with a texture analyzer. Dissolution was performed using USP 26 apparatus II modified by insertion of a mesh to prevent sticking of tablets to the bottom of the vessel and to allow free three-dimensional matrix swelling. Significant release differences between tablet batches were observed and this was consistent with changes in swelling rate, gel thickness, and swelling front movement within the tablets. Matrices containing approximately 30% drug load and water-soluble lactose, demonstrated more pronounced swelling front movement and hence drug release relative to the matrix tablets containing dicalcium phosphate dihydrate. The observed differences in release were verified by calculating the similarity and difference factors. The interdependence of front movement and mass erosion in relation to excipient types on progression of swelling front movement and alteration of water penetration, erosion, and drug release are explained. It is concluded that unlike in conventional dosage forms inclusion of excipients in hydrophilic controlled-release tablets containing water-soluble drugs should be carefully analyzed as their various physico-chemical properties may have significant implications on swelling dynamics, front movement, drug release kinetics, and consequently in vivo performance.
研究了水溶性和水不溶性辅料对含水溶性药物的亲水性基质片剂的水化动力学、前沿移动、溶蚀及药物释放的影响。片剂采用直接压片法制备，并用质构分析仪评估其无约束溶胀行为和凝胶强度。溶出试验使用经改良的USP 26装置II进行，通过插入筛网防止片剂粘在容器底部，并使基质能够自由进行三维溶胀。观察到不同批次片剂之间存在显著的释放差异，这与片剂内部溶胀速率、凝胶厚度和溶胀前沿移动的变化一致。相对于含有二水磷酸氢钙的基质片剂，含约30%药物负载量和水溶性乳糖的基质表现出更明显的溶胀前沿移动，从而药物释放也更明显。通过计算相似性和差异因子验证了观察到的释放差异。解释了溶胀前沿移动与质量溶蚀的相互关系，以及辅料类型对溶胀前沿移动进程、水分渗透、溶蚀和药物释放改变的影响。得出结论，与传统剂型不同，在含水溶性药物的亲水性控释片剂中加入辅料时应仔细分析，因为其各种物理化学性质可能对溶胀动力学、前沿移动、药物释放动力学以及体内性能产生重大影响。
