Analysis of the Effects of Process Parameters on Start-Up Operation in Continuous Wet Granulation
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Manufacturing Methods
2.3. Characterization Methods
2.4. Assessment Methods
2.4.1. Torque Profile
2.4.2. Granule Size Distribution
- Visual comparison.
- Tenth-percentile, median, and ninth-percentile diameter.
- Fractions of fines and oversized granules, or granulation yield.
- Fitting by probability distributions, e.g., Gaussian distribution.
- Multivariate analysis.
2.4.3. Cost Analysis
3. Results and Discussion
3.1. Assessment of Torque Profile
3.2. Assessment of Granule Size Distribution
3.3. Economic Assessment with Different Start-Up Criteria
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
API | active pharmaceutical ingredient |
DoE | design of experiments |
HPMC | hydroxypropylmethylcellulose |
L/D | length-to-diameter |
L/S | liquid-to-solid |
PAT | process analytical technology |
PC | principal component |
PCA | principal component analysis |
RBF | radial basis function |
RMSE | root mean square error |
Nomenclature | |
Variable | Description |
cest | estimated coefficient for each parameter |
Celec | electricity price [USD KWh−1] |
Cenergy | energy cost [USD lot−1] |
Cmaterial | raw material cost [USD lot–1] |
CRM | unit price of raw materials [USD kg−1] |
CWG | cost of wet granulation [USD lot−1] |
mlot | lot size [kg lot−1] |
r | screw speed [rpm] |
SE | standard error of the coefficient cest |
t | running time [min] |
T | torque [N m] |
tdead | dead time [min] |
Tend | terminal torque [N m] |
tstart | time needed for a start-up operation [h lot−1] |
tstat | t-statistic [–] |
T0 | initial torque [N m] |
v | manufacturing rate [kg h−1] |
α | liquid-to-solid ratio [–] |
γ | hyperparameter in RBFs |
σ | hyperparameter in RBFs |
τ | time constant [min] |
φ | RBFs |
Appendix A
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Component | Substance | Composition [% (w/w)] |
---|---|---|
API | Theophylline | 5.0 |
Filler | α-lactose monohydrate | 65.0 |
Filler | Microcrystalline cellulose | 15.0 |
Binder | Hydroxypropylmethylcellulose | 15.0 |
Experiment | Manufacturing Rate v [kg h–1] | Screw Speed r [rpm] | L/S Ratio α [–] |
---|---|---|---|
N1 | 5.0 | 500 | 0.12 |
N2 | 5.0 | 500 | 0.16 |
N3 | 5.0 | 900 | 0.12 |
N4 | 5.0 | 900 | 0.16 |
N5 | 20.0 | 500 | 0.12 |
N6 | 20.0 | 500 | 0.16 |
N7 | 20.0 | 900 | 0.12 |
N8 | 20.0 | 900 | 0.16 |
N9 | 12.5 | 700 | 0.14 |
N10 | 12.5 | 700 | 0.14 |
Experiment | T0 [N m] | Tend [N m] | τ [min] | tdead [min] | RMSE |
---|---|---|---|---|---|
N1 | 1.61 | 3.43 | 20.7 | 8.84 | 0.0775 |
N2 | 1.95 | 7.44 | 7.80 | 4.30 | 0.1765 |
N3 | 1.40 | 3.91 | 44.1 | 2.89 × 10−14 | 0.0793 |
N4 | 1.99 | 5.04 | 4.08 | 2.62 | 0.1776 |
N5 | 2.10 | 4.30 | 60.0 | 20.8 | 0.0900 |
N6 | 7.69 | 12.3 | 3.34 | 3.31 | 0.7117 |
N7 | 2.09 | 2.86 | 11.0 | 1.05 × 10−15 | 0.0407 |
N8 | 2.04 | 6.86 | 12.8 | 7.47 × 10−15 | 0.1823 |
N9 | 2.36 | 4.62 | 60.0 | 1.75 × 10−13 | 0.1643 |
N10 | 2.15 | 3.01 | 5.70 | 7.68 | 0.1312 |
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Matsunami, K.; Ryckaert, A.; Peeters, M.; Badr, S.; Sugiyama, H.; Nopens, I.; De Beer, T. Analysis of the Effects of Process Parameters on Start-Up Operation in Continuous Wet Granulation. Processes 2021, 9, 1502. https://doi.org/10.3390/pr9091502
Matsunami K, Ryckaert A, Peeters M, Badr S, Sugiyama H, Nopens I, De Beer T. Analysis of the Effects of Process Parameters on Start-Up Operation in Continuous Wet Granulation. Processes. 2021; 9(9):1502. https://doi.org/10.3390/pr9091502
Chicago/Turabian StyleMatsunami, Kensaku, Alexander Ryckaert, Michiel Peeters, Sara Badr, Hirokazu Sugiyama, Ingmar Nopens, and Thomas De Beer. 2021. "Analysis of the Effects of Process Parameters on Start-Up Operation in Continuous Wet Granulation" Processes 9, no. 9: 1502. https://doi.org/10.3390/pr9091502