A New Validation Methodology for In Silico Tools Based on X-ray Computed Tomography Images of Tablets and a Performance Analysis of One Tool.

Sebastian Bollmann,Peter Kleinebudde

doi:10.3390/pharmaceutics13091488

Abstract

In silico tools which predict the dissolution of pharmaceutical dosage forms using virtual matrices can be validated with virtual matrices based on X-ray micro-computed tomography images of real pharmaceutical formulations. Final processed images of 3 different tablet batches were used to check the performance of the in silico tool F-CAD. The goal of this work was to prove the performance of the software by comparing the predicted dissolution profiles to the experimental ones and to check the feasibility and application of the validation concept for in silico tools. Both virtual matrices based on X-ray micro-computed tomography images and designed by the software itself were used. The resulting dissolution curves were compared regarding their similarity to the experimental curve. The kinetics were analysed with the Higuchi and Korsmeyers–Peppas plot. The whole validation concept as such was feasible and worked well. It was possible to identify prediction errors of the software F-CAD and issues with the virtual tablets designed within the software.

Highlights

In 2004, the American Food and Drug Administration (FDA) started the ProcessAnalytical Technology initiative to transform the art of pharmaceutical development and processes to science with the goal of quality by design [1]
The virtual tablets produced by the the PAC-module of F-CAD did not represent the real tablets
The predicted dissolution profiles were significantly different from the experimental profiles and the XμCT image based predicted profiles

Summary

Introduction

In 2004, the American Food and Drug Administration (FDA) started the Process. Analytical Technology initiative to transform the art of pharmaceutical development and processes to science with the goal of quality by design [1]. Since the concept was revised several times. The International Council of Harmonisation adopted the concept for several guidelines [2,3]. An increasing number of in silico tools to support the pharmaceutical development is available. A complete in silico development of pharmaceutical dosage forms does not seem possible at the present time. In silico tools may contribute to cost reduction and saving of development time in the future

Objectives

Methods

Results

Conclusion