title: Prediction of drug content and hardness of intact tablets using artificial neural network and near-infrared spectroscopy.
abstract: The purpose of this study was to predict drug content and hardness of intact tablets using artificial neural networks (ANN) and near-infrared spectroscopy (NIRS). Tablets for the drug content study were compressed from mixtures of Avicel PH-101, 0.5% magnesium stearate, and varying concentrations (0%, 1%, 2%, 5%, 10%, 20%, and 40% w/w) of theophylline. Tablets for the hardness study were compressed from mixtures of Avicel PH-101 and 0.5% magnesium stearate at varying compression forces ranging from 0.4 to 1 ton. An Intact Analyzer was used to obtain near infrared spectra from the tablets with varying drug contents, whereas a Rapid Content Analyzer (RCA) was used to obtain spectral data from the tablets with varying hardness. Two sets of tablets from each batch (i.e., tablets with varying drug content and hardness) were randomly selected. One set of tablets was used to generate appropriate calibration models, while the other set was used as the unknown (test) set. A total of 10 ANN calibration models (5 each with 10 and 160 inputs at appropriate wavelengths) and five separate 4-factor partial least squares (PLS) calibration models were generated to predict drug contents of the test tablets from the spectral data. For the prediction of tablet hardness, two ANN calibration models (one each with 10 and 160 inputs) and two 4-factor PLS calibration models were generated and used to predict the hardness of test tablets. The PLS calibration models were generated using Vision software. Prediction of drug contents of test tablets using the ANN calibration models generated with 10 inputs was significantly better than the prediction obtained with the ANN calibration models with 160 inputs. For tablets with low drug concentrations (less than or equal to 2% w/w) prediction of drug content was better with either of the two ANN calibration models than with the PLS calibration models. However, prediction of drug contents of tablets with greater than or equal to 5% w/w drug was better with the PLS calibration models than with the ANN calibration models. Prediction of tablet hardness was better with the ANN calibration models generated with either 10 or 160 inputs than with the PLS calibration models. This work demonstrated that a well-trained ANN model is a powerful alternative technique for analysis of NIRS data. Moreover, the technique could be used in instances when the conventional modeling of data does not work adequately.
authors.affiliation: Boehringer Ingelheim Vetmedica, Inc, St Joseph, Missouri, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.forename: S S
authors.initials: SS
authors.lastname: Thosar
authors.forename: R A
authors.initials: RA
authors.lastname: Forbess
authors.forename: M S
authors.initials: MS
authors.lastname: Kemper
authors.forename: R L
authors.initials: RL
authors.lastname: Rubinovitz
authors.forename: A J
authors.initials: AJ
authors.lastname: Shukla
mesh_terms: D002138:Calibration; D002626:Chemistry, Pharmaceutical; D006245:Hardness Tests; D008962:Models, Theoretical; D016571:Neural Networks, Computer; D004364:Pharmaceutical Preparations / Q000032:analysis*; D011237:Predictive Value of Tests; D019265:Spectroscopy, Near-Infrared; D013607:Tablets
chemical_list: D004364:Pharmaceutical Preparations; D013607:Tablets