Borgquist Per, Nevsten Pernilla, Nilsson Bernt, Wallenberg L Reine, Axelsson Anders
Department of Chemical Engineering, Lund University, P.O. Box 124, SE-221 00 Lund, Sweden.
J Control Release. 2004 Jul 7;97(3):453-65. doi: 10.1016/j.jconrel.2004.03.024.
A previously described single-pellet release model has been simplified and modified to give predictions of the release from multiple-pellet systems, besides describing the release from single pellets. The simplified single-pellet model has been verified using single-pellet data and has been used to estimate three release-controlling parameters, namely the pellet core radius, the overall mass transfer coefficient, and the lag time. Single-pellet release experiments showed that the release from the individual film-coated drug cores resulted in a wide distribution of release profiles, a phenomenon not observed on the dose level. Therefore, the parameter estimations resulted in distributions of these parameter values. The core radius and the lag times compared well with the experimental data. The distributions were used as input data for the multiple pellet model, in order to predict the release profiles on the dose level, showing results consistent with the measured dose release. The dose-predictive ability of the model was demonstrated in simulations by studying the effect of a change in the size of the single subunits (of constant total dose), showing that smaller pellets give an increased release rate with less variation. The model for predicting dose-release profiles could be of great value in optimising the performance of an existing formulation, as well as in the development of a new controlled-release pharmaceutical.
一个先前描述的单丸剂释放模型已被简化和修改，以便除了描述单丸剂的释放情况外，还能预测多丸剂系统的释放情况。简化后的单丸剂模型已通过单丸剂数据进行验证，并已用于估计三个释放控制参数，即丸芯半径、总传质系数和滞后时间。单丸剂释放实验表明，单个薄膜包衣药物丸芯的释放导致释放曲线分布广泛，这一现象在剂量水平上未观察到。因此，参数估计得出了这些参数值的分布。丸芯半径和滞后时间与实验数据比较吻合。这些分布被用作多丸剂模型的输入数据，以便预测剂量水平上的释放曲线，结果显示与测量的剂量释放一致。通过研究单亚基（总剂量恒定）尺寸变化的影响，在模拟中证明了该模型的剂量预测能力，结果表明较小的丸剂释放速率增加且变化较小。预测剂量释放曲线的模型在优化现有制剂的性能以及开发新型控释药物方面可能具有很大价值。
