Mandal Uttam, Gowda Veeran, Ghosh Animesh, Bose Anirbandeep, Bhaumik Uttam, Chatterjee Bappaditya, Pal Tapan Kumar
Bioequivalence Study Centre, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India.
Chem Pharm Bull (Tokyo). 2008 Feb;56(2):150-5. doi: 10.1248/cpb.56.150.
The aim of the present study was to apply the simultaneous optimization method incorporating Artificial Neural Network (ANN) using Multi-layer Perceptron (MLP) model to the development of a metformin HCl 500 mg sustained release matrix tablets with an optimized in vitro release profile. The amounts of HPMC K15M and PVP K30 at three levels (-1, 0, +1) for each were selected as casual factors. In vitro dissolution time profiles at four different sampling times (1 h, 2 h, 4 h and 8 h) were chosen as output variables. 13 kinds of metformin matrix tablets were prepared according to a 2(3) factorial design (central composite) with five extra center points, and their dissolution tests were performed. Commercially available STATISTICA Neural Network software (Stat Soft, Inc., Tulsa, OK, U.S.A.) was used throughout the study. The training process of MLP was completed until a satisfactory value of root square mean (RSM) for the test data was obtained using feed forward back propagation method. The root mean square value for the trained network was 0.000097, which indicated that the optimal MLP model was reached. The optimal tablet formulation based on some predetermined release criteria predicted by MLP was 336 mg of HPMC K15M and 130 mg of PVP K30. Calculated difference (f(1) 2.19) and similarity (f(2) 89.79) factors indicated that there was no difference between predicted and experimentally observed drug release profiles for the optimal formulation. This work illustrates the potential for an artificial neural network with MLP, to assist in development of sustained release dosage forms.
本研究的目的是将结合人工神经网络(ANN)的同时优化方法与多层感知器(MLP)模型应用于盐酸二甲双胍500mg缓释骨架片的研发,以优化其体外释放曲线。将HPMC K15M和PVP K30的三个水平(-1、0、+1)的用量作为随机因素。选择四个不同取样时间(1小时、2小时、4小时和8小时)的体外溶出时间曲线作为输出变量。根据具有五个额外中心点的2(3)析因设计(中心复合设计)制备了13种二甲双胍骨架片,并进行了溶出度试验。在整个研究过程中使用了市售的STATISTICA神经网络软件(Stat Soft公司,美国俄克拉何马州塔尔萨)。使用前馈反向传播方法完成MLP的训练过程,直到获得测试数据的令人满意的均方根(RSM)值。训练网络的均方根值为0.000097,这表明达到了最佳MLP模型。基于MLP预测的一些预定释放标准的最佳片剂配方为336mg HPMC K15M和130mg PVP K30。计算得到的差异(f(1) 2.19)和相似性(f(2) 89.79)因子表明,最佳配方的预测药物释放曲线与实验观察到的药物释放曲线之间没有差异。这项工作说明了具有MLP的人工神经网络在协助开发缓释剂型方面的潜力。