Process Model Approach to Predict Tablet Weight Variability for Direct Compression Formulations at Pilot and Production Scale

Raghu V G Peddapatla,Zelalem A Worku,Clare O’Reilly,Ivan Browning,Gerard Sheridan,Abina M Crean,Shrikant Swaminathan,Conor Slevin,Stephen Sheehan,David Egan

doi:10.3390/pharmaceutics13071033

Raghu V G Peddapatla, Zelalem A Worku + Show 8 more

Open Access

https://doi.org/10.3390/pharmaceutics13071033

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Abstract

Optimizing processing conditions to achieve a critical quality attribute (CQA) is an integral part of pharmaceutical quality by design (QbD). It identifies combinations of material and processing parameters ensuring that processing conditions achieve a targeted CQA. Optimum processing conditions are formulation and equipment-dependent. Therefore, it is challenging to translate a process design between formulations, pilot-scale and production-scale equipment. In this study, an empirical model was developed to determine optimum processing conditions for direct compression formulations with varying flow properties, across pilot- and production-scale tablet presses. The CQA of interest was tablet weight variability, expressed as percentage relative standard deviation. An experimental design was executed for three model placebo blends with varying flow properties. These blends were compacted on one pilot-scale and two production-scale presses. The process model developed enabled the optimization of processing parameters for each formulation, on each press, with respect to a target tablet weight variability of <1%RSD. The model developed was successfully validated using data for additional placebo and active formulations. Validation formulations were benchmarked to formulations used for model development, employing permeability index values to indicate blend flow.

Highlights

SSPC Pharmaceutical Research Centre, School of Pharmacy, University College Cork, T12 K8AF Cork, Ireland; Pharmaceutical Manufacturing Technology Centre (PMTC), Bernal Institute, University of Limerick, Abstract: Optimizing processing conditions to achieve a critical quality attribute (CQA) is an integral part of pharmaceutical quality by design (QbD)
The study presented demonstrates the development of a process model to predict tablet weight variability, expressed as %RSD, for direct compression formulations with varying flow properties, across pilot- and production-scale tablet presses
The resulting model and formulation–tablet press-specific optimum process conditions provided a comprehensive overview of the behaviour of direct compression formulations with varying flow behaviour across a range of press types

Summary

Introduction

SSPC Pharmaceutical Research Centre, School of Pharmacy, University College Cork, T12 K8AF Cork, Ireland; Pharmaceutical Manufacturing Technology Centre (PMTC), Bernal Institute, University of Limerick, Abstract: Optimizing processing conditions to achieve a critical quality attribute (CQA) is an integral part of pharmaceutical quality by design (QbD). An empirical model was developed to determine optimum processing conditions for direct compression formulations with varying flow properties, across pilot- and production-scale tablet presses. Introduction with regard to jurisdictional claims in Direct compression is a relatively simple method to manufacture pharmaceutical tablets It involves two primary processing steps, viz., blending and compaction and is less complicated compared to tablet production involving a dry granulation or wet granulation step [1]. To produce tablets of sufficient quality at production scale, direct compression formulations are required to exhibit adequate flow, blend uniformity, compaction and ease of ejection from the tablet press [1,2,3,4,5]. The relationship between press speed, feed frame design and speed, and formulation flow properties influences the die filling process and the quality of the tablets produced [9,12]

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