Development of a Granule Growth Regime Map for Twin Screw Wet Granulation Process via Data Imputation Techniques
Abstract
:1. Introduction
Objectives
2. Background
2.1. Data Completion Methods
2.2. Granulation Regime Maps
3. Methods
3.1. Data Acquisition
Inputs and Outputs
3.2. Data Imputation Techniques
3.2.1. First-Principle Based Data Completion
3.2.2. Statistical Data Completion Techniques
3.3. Regime Map Formulation
3.3.1. X-axis
3.3.2. Y-axis
4. Results and Discussion
4.1. Missing Data Completion
4.2. Region Identification on the Granule Growth Regime Map
- At very low x-axis values of the proposed regime map, the binder content is very low, and no granules are formed. This region was named the “Under-wetted” region. Close to the right extreme of this x-axis value range, at high there could be formation of crumb-like material due to Van der Waal and other such dry surface adhesion phenomena, this region falls under “Crumb”.
- At a slightly greater (estimated to be around 0.07 based on Iveson et al.’s work [24]) and at low , due to the lack of sufficient binder to form adequate nuclei the resulting granule size distribution is observed to have bi-modal distribution with a large percentage of fine particles and a relatively higher amount of loosely formed large particles. This is typical of nucleation dominant growth and hence, this region was named “Nucleation”.
- In this range of and at high the loosely formed large particles undergo breakage and ultimately crumb-like material formation occurs. This region was also named “Crumb”.
- When the is further increased, sufficient binder becomes available to form more nuclei. Under such conditions, one of the following phenomena occurs depending on the value.
- –
- At very low , due to a lack of sufficient energy for successful coalescence the granules will grow via layering mechanism. In previous work, Kotamarthy et al. [6] showed that the axial mixing and the collisions are affected by the energy supplied to the system, which is directly proportional to the mixing efficiency. Due to poor mixing and low shear conditions, these process and equipment settings can lead to the formation of bi-modal size distributions characterized by the formation of relatively smaller and weaker (higher porosity) granules. This is named “Type A/Layering dominant granulation”.
- –
- At higher , there is sufficient energy to squeeze the binder liquid to the surface of the granules leading to further coalescence and growth (Type II coalescence). Due to enhanced mixing and promotion of coalescence, granulation under these conditions will result in a relatively uni-modal particle size distribution. Moreover, due to extensive coalescence, the granules formed under these conditions will be highly dense and relatively large. This region was named “Type B/coalescence driven granulation”.
- When the is increased further there is sufficient binder liquid present around the initial granules formed to promote coalescence type growth (Type I coalescence) irrespective of the energy provided. Such settings will lead to the formation of very large granules. This region will still fall under “Type B/coalescence driven granulation”.
- Very high will result in the formation of paste-like material. This region was named “Slurry”.
4.3. Effect of Twin-Screw Granulation Parameters
4.3.1. Effect of Screw Speed
4.3.2. Effect of Feed Rate
4.3.3. Effect of Liquid to Solid Ratio
4.3.4. Effect of Binder Viscosity
4.3.5. Effect of Kneading Elements
4.3.6. Effect of Stagger Angle
4.3.7. Effect of Primary Powder Properties
4.4. Validation of Developed Regime Map
4.5. Analysis of The-Breakage-Dominant Growth
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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No. | Author | Granulator Size (mm) | Process Parameters Varied | Material Properties Varied | No. of Screw Configurations Used | No. of Experiments Performed |
---|---|---|---|---|---|---|
1 | Dhenge et al., 2012 [5] | 16 | L/S Ratio | Binder viscosity | 1 | 9 |
2 | Vercruysse et al., 2012 [35] | 25 | Flow Rate | |||
RPM | – | 6 | 18 | |||
Temperature | ||||||
3 | Dhenge et al., 2013 [19] | 16 | Flow Rate | Binder viscosity | 1 | 9 |
4 | Meier et al., 2013 [36] | 16 | Flow Rate RPM | – | 1 | 14 |
5 | Kumar et al., 2016 [15] | 25 | Flow Rate | |||
RPM | Binder viscosity | 2 | 54 | |||
L/S Ratio | ||||||
6 | Mundozah et al., 2020 [28] | 16 | RPM | Bulk Solid | 3 | 28 |
Total | 132 |
Input Parameters | Outputs Parameters | ||
---|---|---|---|
Geometry | Process | Material | |
Number of CE and KE | L/S ratio | Initial PSD | Granule size distribution (GSD) |
Staggering angle of KE | Screw Speed (RPM) | Viscosity of binder | Torque |
L/D ratio | Feed rate | % API in powder | % fill of barrel |
Granulator diameter | Temperature | Mean residence time | |
Liquid addition position |
Process Parameters | Binder Liquid Paramters | Screw Parameters | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Screw Speed | Feed Rate | L/S Ratio | Binder Viscosity | Kneading Elements | Stagger Angle | ||||||||
Parameters | D | I | D | I | D | I | D | I | D | I | D | I | |
x-axis | L/S Ratio | + | |||||||||||
Binder Viscosity | + | ||||||||||||
y-axis | Screw Speed | + | |||||||||||
Torque | - | + | + | + | + | + | |||||||
Feed Rate | + | ||||||||||||
MRT | - | + | + | + | + | + | |||||||
+ | - | - | |||||||||||
Contact Ratio | + | - | + | + | + | + |
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Kotamarthy, L.; Sampat, C.; Ramachandran, R. Development of a Granule Growth Regime Map for Twin Screw Wet Granulation Process via Data Imputation Techniques. Pharmaceutics 2022, 14, 2211. https://doi.org/10.3390/pharmaceutics14102211
Kotamarthy L, Sampat C, Ramachandran R. Development of a Granule Growth Regime Map for Twin Screw Wet Granulation Process via Data Imputation Techniques. Pharmaceutics. 2022; 14(10):2211. https://doi.org/10.3390/pharmaceutics14102211
Chicago/Turabian StyleKotamarthy, Lalith, Chaitanya Sampat, and Rohit Ramachandran. 2022. "Development of a Granule Growth Regime Map for Twin Screw Wet Granulation Process via Data Imputation Techniques" Pharmaceutics 14, no. 10: 2211. https://doi.org/10.3390/pharmaceutics14102211
APA StyleKotamarthy, L., Sampat, C., & Ramachandran, R. (2022). Development of a Granule Growth Regime Map for Twin Screw Wet Granulation Process via Data Imputation Techniques. Pharmaceutics, 14(10), 2211. https://doi.org/10.3390/pharmaceutics14102211