Design Space Approach in Optimization of Fluid Bed Granulation and Tablets Compression Process

Jelena Djuriš,Ivana Vasiljević,Marko Krstić,Svetlana Ibrić,Djordje Medarević,Ivana Mašić

doi:10.1100/2012/185085

Jelena Djuriš, Ivana Vasiljević + Show 4 more

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https://doi.org/10.1100/2012/185085

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Journal: TheScientificWorldJournal	Publication Date: Jan 1, 2012
Citations: 11	License type: CC BY 3.0

Affiliation: University of Belgrade

Abstract

The aim of this study was to optimize fluid bed granulation and tablets compression processes using design space approach. Type of diluent, binder concentration, temperature during mixing, granulation and drying, spray rate, and atomization pressure were recognized as critical formulation and process parameters. They were varied in the first set of experiments in order to estimate their influences on critical quality attributes, that is, granules characteristics (size distribution, flowability, bulk density, tapped density, Carr's index, Hausner's ratio, and moisture content) using Plackett-Burman experimental design. Type of diluent and atomization pressure were selected as the most important parameters. In the second set of experiments, design space for process parameters (atomization pressure and compression force) and its influence on tablets characteristics was developed. Percent of paracetamol released and tablets hardness were determined as critical quality attributes. Artificial neural networks (ANNs) were applied in order to determine design space. ANNs models showed that atomization pressure influences mostly on the dissolution profile, whereas compression force affects mainly the tablets hardness. Based on the obtained ANNs models, it is possible to predict tablet hardness and paracetamol release profile for any combination of analyzed factors.

Highlights

IntroductionProposed quality-bydesign (QbD) regulatory initiative of pharmaceutical product and process development has encouraged researchers in pharmaceutical industry to reach the “desired state” of drug manufacturing in 21st century
The emphasis has changed from the need to demonstrate that the product will consistently meet relatively tight specifications to a new situation of being able to demonstrate that the product is controlled within a broader “design space” (DS)
Characterization of obtained granules was performed after granulation

Summary

Introduction

Proposed quality-bydesign (QbD) regulatory initiative of pharmaceutical product and process development has encouraged researchers in pharmaceutical industry to reach the “desired state” of drug manufacturing in 21st century. Main goal of this approach is to gain a comprehensive understanding of their manufacturing processes, with an accurate estimation of their robustness and reliability. The design space (DS) concept is introduced as “the multidimensional combination and interaction of input variables (e.g., materials attributes) and process parameters that have been demonstrated to provide assurance of quality.”. The design space (DS) concept is introduced as “the multidimensional combination and interaction of input variables (e.g., materials attributes) and process parameters that have been demonstrated to provide assurance of quality.” Using this approach, it is essential to define relationship between critical formulation/process parameters and critical quality attributes (such as granule characteristics and tablet properties) [1, 2]

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