Optimization of Salbutamol Sulfate Dissolution from Sustained Release Matrix Formulations Using an Artificial Neural Network

An artificial neural network was used to optimize the release of salbutamol sulfate from hydrophilic matrix formulations. Model formulations to be used for training, testing and validating the neural network were manufactured with the aid of a central composite design with varying the levels of Methocel® K100M, xanthan gum, Carbopol® 974P and Surelease® as the input factors. In vitro dissolution time profiles at six different sampling times were used as target data in training the neural network for formulation optimization. A multi layer perceptron with one hidden layer was constructed using Matlab®, and the number of nodes in the hidden layer was optimized by trial and error to develop a model with the best predictive ability. The results revealed that a neural network with nine nodes was optimal for developing and optimizing formulations. Simulations undertaken with the training data revealed that the constructed model was useable. The optimized neural network was used for optimization of formulation with desirable release characteristics and the results indicated that there was agreement between the predicted formulation and the manufactured formulation. This work illustrates the possible utility of artificial neural networks for the optimization of pharmaceutical formulations with desirable performance characteristics.

[1]  L. Maggi,et al.  Matrices containing NaCMC and HPMC 2. Swelling and release mechanism study. , 2007, International journal of pharmaceutics.

[2]  Kozo Takayama,et al.  Multi-objective simultaneous optimization technique based on an artificial neural network in sustained release formulations , 1997 .

[3]  Svetlana Ibrić,et al.  The application of generalized regression neural network in the modeling and optimization of aspirin extended release tablets with Eudragit RS PO as matrix substance. , 2002, Journal of controlled release : official journal of the Controlled Release Society.

[4]  Yixin Chen,et al.  Application of artificial neural networks in the design of controlled release drug delivery systems. , 2003, Advanced drug delivery reviews.

[5]  B. D. Rohera,et al.  Comparative evaluation of rate of hydration and matrix erosion of HEC and HPC and study of drug release from their matrices. , 2002, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[6]  P. Calverley,et al.  Modern treatment of chronic obstructive pulmonary disease , 2001, European Respiratory Journal.

[7]  J. W. Moore,et al.  Mathematical comparison of dissolution profiles , 1996 .

[8]  S. Rani,et al.  Formulation and Evaluation of Controlled-Release Transdermal Patches of Theophylline–Salbutamol Sulfate , 2001, Drug development and industrial pharmacy.

[9]  T Nagai,et al.  Formula optimization of theophylline controlled-release tablet based on artificial neural networks. , 2000, Journal of controlled release : official journal of the Controlled Release Society.

[10]  S. Baveja,et al.  Zero-order release hydrophilic matrix tablets of β-adrenergic blockers , 1987 .

[11]  G. Jayasagar,,et al.  Formulation and Evaluation of Diclofenac Sodium Using Hydrophilic Matrices , 2001, Drug development and industrial pharmacy.

[12]  M C Meyer,et al.  The application of an artificial neural network and pharmacokinetic simulations in the design of controlled-release dosage forms. , 1999, Journal of controlled release : official journal of the Controlled Release Society.

[13]  J. Schwartz,et al.  Studies on Drug Release from a Carbomer Tablet Matrix , 1995 .

[14]  Sean C. Sweetman,et al.  Martindale: The Complete Drug Reference , 1999 .

[15]  S. Baveja,et al.  Sustained release tablet formulation of centperazine , 1986 .

[16]  Peter York,et al.  Optimisation of the predictive ability of artificial neural network (ANN) models: a comparison of three ANN programs and four classes of training algorithm. , 2005, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[17]  J Bourquin,et al.  Comparison of artificial neural networks (ANN) with classical modelling techniques using different experimental designs and data from a galenical study on a solid dosage form. , 1998, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[18]  J. Sousa,et al.  Role of Cellulose Ether Polymers on Ibuprofen Release from Matrix Tablets , 2005, Drug development and industrial pharmacy.

[19]  Ping I. Lee Diffusional release of a solute from a polymeric matrix — approximate analytical solutions , 1980 .

[20]  Kozo Takayama,et al.  Neural network based optimization of drug formulations. , 2003, Advanced drug delivery reviews.

[21]  G. Khan,et al.  Formulation and in vitro evaluation of ibuprofen-Carbopol 974P-NF controlled release matrix tablets. III: Influence of co-excipients on release rate of the drug. , 1998, Journal of controlled release : official journal of the Controlled Release Society.

[22]  Martin H. Abramson,et al.  Complete Drug Reference , 1996 .

[23]  Y Obata,et al.  Simultaneous optimization based on artificial neural networks in ketoprofen hydrogel formula containing O-ethyl-3-butylcyclohexanol as percutaneous absorption enhancer. , 2001, Journal of pharmaceutical sciences.

[24]  Rajiv Kumar,et al.  Optimizing drug delivery systems using systematic "design of experiments." Part I: fundamental aspects. , 2005, Critical reviews in therapeutic drug carrier systems.

[25]  Robert D. Johnson,et al.  Application of Neural Computing in Pharmaceutical Product Development , 1991, Pharmaceutical Research.

[26]  D. L. Munday,et al.  Relationship between swelling, erosion and drug release in hydrophillic natural gum mini-matrix formulations. , 1998, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[27]  J. Siepmann,et al.  Hydrophilic Matrices for Controlled Drug Delivery: An Improved Mathematical Model to Predict the Resulting Drug Release Kinetics (the “sequential Layer” Model) , 2004, Pharmaceutical Research.

[28]  Christopher T. Rhodes,et al.  Artificial Neural Networks: Implications for Pharmaceutical Sciences , 1995 .

[29]  Franc Vrecer,et al.  Optimization of diclofenac sodium dissolution from sustained release formulations using an artificial neural network , 1997 .

[30]  M. Durrani,et al.  Studies on Drug Release Kinetics from Carbomer Matrices , 1994 .

[31]  R. Erb,et al.  Introduction to Backpropagation Neural Network Computation , 1993, Pharmaceutical Research.

[32]  J. Zhu,et al.  Ibuprofen release kinetics from controlled-release tablets granulated with aqueous polymeric dispersion of ethylcellulose II: influence of several parameters and coexcipients. , 1998, Journal of controlled release : official journal of the Controlled Release Society.

[33]  R. Kinget,et al.  Comparative study on xanthan gum and hydroxypropylmethyl cellulose as matrices for controlled-release drug delivery I. Compaction and in vitro drug release behaviour , 1996 .

[34]  J. Parojčić,et al.  Artificial neural networks in the modeling and optimization of aspirin extended release tablets with eudragit L 100 as matrix substance , 2008, AAPS PharmSciTech.

[35]  T. Tsai,et al.  Film-forming polymer-granulated excipients as the matrix materials for controlled release dosage forms. , 1998, Journal of controlled release : official journal of the Controlled Release Society.

[36]  T Nagai,et al.  Formula optimization based on artificial neural networks in transdermal drug delivery. , 1999, Journal of controlled release : official journal of the Controlled Release Society.

[37]  Nicholas A. Peppas,et al.  Modelling of drug diffusion through swellable polymeric systems , 1980 .

[38]  C. Ferrero,et al.  Compaction properties, drug release kinetics and fronts movement studies from matrices combining mixtures of swellable and inert polymers: effect of HPMC of different viscosity grades. , 2008, International journal of pharmaceutics.