TY - JOUR
T1 - Modelling the Compaction Step of a Platform Direct Compression Process
AU - Peddapatla, Raghu V.G.
AU - Slevin, Conor
AU - Sheridan, Gerard
AU - Beirne, Caoimhe
AU - Swaminathan, Shrikant
AU - Browning, Ivan
AU - O’reilly, Clare
AU - Worku, Zelalem A.
AU - Egan, David
AU - Sheehan, Stephen
AU - Crean, Abina M.
N1 - Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/4
Y1 - 2022/4
N2 - The ability to predict formulation behaviour at production scale during formulation design can reduce the time to market and decrease product development costs. However, it is challenging to extrapolate compaction settings for direct compression formulations between tablet press models during scale-up and transfer from R&D to commercial production. The aim of this study was to develop statistical process models to predict tablet tensile strength, porosity and disintegration time from compaction parameters (pre-compression and main compression force, and press speed), for three formulations, with differing deformation characteristics (plastic, brittle and elastic), on three tablet press models (one pilot-scale tablet press (KG RoTab) and two production-scale presses (Fette 1200i and GEA Modul P)). The deformation characteristics of yield pressure and elastic recovery were determined for the model placebo formulations investigated. To facilitate comparison of dwell time settings between tablet press models, the design of experiments (DoE) approach was 9 individual 16-run response surface DoEs (3 formulation × 3 press models), whose results were combined to create a polynomial regression model for each tablet property. These models predicted tablet tensile strength, porosity and disintegration time and enabled the construction of design spaces to produce tablets with specified target properties, for each formulation on each press. The models were successfully validated. This modelling approach provides an understanding of the compaction behaviour of formulations with varying deformation behaviour on development and commercial tablet press models. This understanding can be applied to inform achievable production rates at a commercial scale, during the formulation development.
AB - The ability to predict formulation behaviour at production scale during formulation design can reduce the time to market and decrease product development costs. However, it is challenging to extrapolate compaction settings for direct compression formulations between tablet press models during scale-up and transfer from R&D to commercial production. The aim of this study was to develop statistical process models to predict tablet tensile strength, porosity and disintegration time from compaction parameters (pre-compression and main compression force, and press speed), for three formulations, with differing deformation characteristics (plastic, brittle and elastic), on three tablet press models (one pilot-scale tablet press (KG RoTab) and two production-scale presses (Fette 1200i and GEA Modul P)). The deformation characteristics of yield pressure and elastic recovery were determined for the model placebo formulations investigated. To facilitate comparison of dwell time settings between tablet press models, the design of experiments (DoE) approach was 9 individual 16-run response surface DoEs (3 formulation × 3 press models), whose results were combined to create a polynomial regression model for each tablet property. These models predicted tablet tensile strength, porosity and disintegration time and enabled the construction of design spaces to produce tablets with specified target properties, for each formulation on each press. The models were successfully validated. This modelling approach provides an understanding of the compaction behaviour of formulations with varying deformation behaviour on development and commercial tablet press models. This understanding can be applied to inform achievable production rates at a commercial scale, during the formulation development.
KW - compaction
KW - direct compression
KW - drug development
KW - formulation development
KW - platform process
KW - porosity
KW - process model
KW - process optimisation
KW - tensile strength
UR - http://www.scopus.com/inward/record.url?scp=85127763201&partnerID=8YFLogxK
U2 - 10.3390/pharmaceutics14040695
DO - 10.3390/pharmaceutics14040695
M3 - Article
AN - SCOPUS:85127763201
SN - 1999-4923
VL - 14
JO - Pharmaceutics
JF - Pharmaceutics
IS - 4
M1 - 695
ER -