www.ercforsops.orgNSF Engineering Research

Center for Structured Organic Particulate Systems (C-SOPS)

GOALS AND DELIVERABLES

• Project Goals:• Develop a non-destructive method for dissolution

using NIR spectroscopy• Build a calibration model to predict dissolution

• Deliverables:• Provide a reliable non-destructive method to

predict drug release in one minute

DESCRIPTION

• The dissolution test is required in the development, registration, approval and quality control of a solid oral dosage form except where the label says that they are to be chewed. The dissolution test is required by over 500 tablet and capsule products described in the United States Pharmacopeia (USP). The dissolution test is the only test performed in manufacturing with the objective of monitoring whether the product will perform adequately throughout its shelf life. The dissolution test is performed in USP dissolution apparatus suitable for the analysis. The method is not suitable for predicting in vivo, but is used for batch-to-batch comparisons.

• The purpose of this assessment is to use NIR spectroscopy (diffuse reflectance ) in combination with multivariate data analysis to predict dissolution properties of the samples in real time. A set of acetaminophen tablets with different shear levels are being studied. All the spectra were pretreated with a baseline correction to maintain the effects of scattering related to tablet physical properties.

METHOD DEVELOPMENT

RESULTS

RESULTS

RESEARCH RELATION TO ERCTest Bed 1:

Tablet Manufacturing

Test Be 2: Strip Film

Test Bed 3: Multi-layer

products

Thrust A: Materials Formation &

Characterization

Thrust B: Design, Scale up, &

Optimization of Manufacturing Processes

Thrust C: Structural Characterization

& Modeling of Products

Thrust D:

Integrated Systems Science

APAP Tablet Description

Mixing

Tableting

ShearingNIR Spectroscopy

Dissolution Test

Instrument Response Reference Values

Multivariate Data Analysis (PCA, PLS-2)

Presenter(S): Eduardo Hernandez, UPRM Research Participants: Pallavi Pawar (Rutgers University), Yifan Wang (Rutgers University),Natasha Velez (UPRM), Goldshid Keyvan (Rutgers University), Fernando Muzzio (Rutgers University), Rodolfo Romanach (UPRM), Alberto Cuitino (Rutgers University)

Prediction of Dissolution Profiles by Non-Destructive Near Infrared Spectroscopy in Tablets Subjected to Different Levels of Strain

Absorbance on NIR spectra decrease as shear increases. Drug release decrease as shear increase.

PCA model projection of test set for NIR spectra

PLS-2 calibration model prediction of dissolution of test set (NIR) vs Dissolution Test (USP Apparatus II)

Comparison between dissolution profiles (USP Apparatus II) with the predicted profiles (NIR calibration model) using PCA.

Impact on Testbed (s)Non destructive fast prediction of dissolution at the end of the continuous process.

Conclusions1. PLS regression can be used to predict the dissolution of the tablets at X

time2. Test Set prediction are highly correlated with the reference method

values. Model capable to discriminate variation in manufacturing conditions

Future Work1. Compare Diffuse Reflectance NIR and Transmittance NIR spectroscopic

methods as techniques to predict dissolutionReferences

2. Kukura, J.; Baxter, J. L.; Muzzio, F. J., Shear distribution and variability in the USP Apparatus 2 under turbulent conditions. International journal of pharmaceutics 2004, 279 (1-2), 9-17.

3. S.H. Tabasi, V. Moolchandani, R. Fahmy and S.W. Hoag, "Sustained Release Dosage Forms Dissolution Behavior Prediction: A Study of Matrix Tablets Using NIR Spectroscopy", Int. J. Pharm. 382, 1 (2009)

Correlation coefficient between NIR prediction and USP Apparatus II

Model Evaluation Results