Gil Eddy Castellanos, Colarte Antonio Iraizoz, Bataille Bernard, Caraballo Isidoro
Center of Pharmaceutical Chemistry, Calle 200, esq 21, Atabey, Playa, Havana, Cuba.
AAPS PharmSciTech. 2007 Dec 28;8(4):E115. doi: 10.1208/pt0804115.
The objective of the present work is to estimate for the first time the percolation threshold of a new series of dextran (native dextran of high molecular weight [B110-1-2, Mw = 2 x 10(6)]), in matrices of lobenzarit disodium (LBD) and to apply the obtained result to the design of hydrophilic matrices for the controlled delivery of this drug. The formulations studied were prepared with different amounts of excipient in the range of 20% to 70% wt/wt. Dissolution studies were performed using the paddle method (100 rpm) and one face water uptake measurements were performed using a modified Enslin apparatus. The Higuchi, zero-order, and Hixson-Crowell models as well as the nonlinear regression model were employed as empiric methods to study the release data. Values of diffusion exponent 0.563 < n < 0.786 (Korsmeyer equation) for dissolution profile and water uptake mechanism 0.715 < n < 1 (Davidson and Peppas equation) suggested anomalous or complex mechanisms. On the other hand, the contribution of the relaxation or erosion and of the diffusive mechanism in Peppas-Sahlin equation indicated that the main mechanism for drug delivery from tablets is swelling controlled delivery (K(r)/K(d) < 1). The critical points observed in kinetic parameters above 58.63% vol/vol of native dextran B110-1-2 plus initial porosity in the LBD-dextran matrices with a relative polymer/drug particle size of 4.17 were attributed to the existence of an excipient percolation threshold.
本研究的目的是首次估算一系列新型右旋糖酐(高分子量天然右旋糖酐[B110-1-2,Mw = 2×10⁶])在氯苯扎利二钠(LBD)基质中的渗滤阈值,并将所得结果应用于该药物控释亲水基质的设计。所研究的制剂是用20%至70% wt/wt范围内不同量的辅料制备的。使用桨法(100 rpm)进行溶出度研究,并使用改良的恩斯林装置进行单面吸水测量。采用Higuchi模型、零级模型、Hixson-Crowell模型以及非线性回归模型作为经验方法来研究释放数据。溶出曲线的扩散指数值0.563 < n < 0.786(Korsmeyer方程)和吸水机制的扩散指数值0.715 < n < 1(Davidson和Peppas方程)表明存在异常或复杂机制。另一方面,Peppas-Sahlin方程中松弛或侵蚀以及扩散机制的贡献表明,片剂药物释放的主要机制是溶胀控释(K(r)/K(d) < 1)。在天然右旋糖酐B110-1-2体积分数高于58.63%加上LBD-右旋糖酐基质中的初始孔隙率且聚合物/药物颗粒相对尺寸为4.17时观察到的动力学参数临界点,归因于辅料渗滤阈值的存在。