High Drug Loading of Amorphous Solid Dispersion by Hot Melt Extrusion: The Role of Magnesium Aluminometasilicate (Neusilin® US2)
Abstract
1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Preparation of Physical Blends
2.3. Hot Melt Extrusion (HME)
2.4. Modulated Differential Scanning Calorimetry (mDSC)
2.5. Powder X-Ray Diffraction (PXRD)
2.6. Downstream Processing
2.6.1. Milling and Particle Size Distribution
2.6.2. Blending for Roller Compaction Process (Intra-Granular Portion)
2.6.3. Compressibility, Tabletability, and Compactability (CTC) Profile
2.6.4. Dry Granulation by Roller Compaction
2.6.5. Characterization of Blend
2.6.6. Final Blending and Tablet Compression
2.7. Characterization of Tablets
2.7.1. Weight Variation, Thickness, Hardness, Friability, Disintegration
2.7.2. Assay and High-Performance Liquid Chromatography (HPLC)
2.7.3. In Vitro Drug Release
2.7.4. mDSC and Fourier Transform Infrared Spectroscopy (FTIR)
2.8. Stability Studies
3. Results and Discussion
3.1. Hot Melt Extrusion Process
3.2. Characterization of HME Extrudates
3.3. CTC Profile
3.4. Roller Compaction and Characterization of Milled Ribbons
3.5. Compression of Tablets and Characterization
3.6. In Vitro Dissolution Profiles
3.7. DSC and FTIR
3.8. Stability Studies
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Formulation# | EZB (%w/w) | Kollidon VA 64 (%) | Neusilin US2 (%) |
---|---|---|---|
F-001 | 10 | 90 | - |
F-002 | 20 | 80 | - |
F-003 | 30 | 70 | - |
F-004 | 30 | 60 | 10 |
F-005 | 40 | 50 | 10 |
F-006 | 40 | 45 | 15 |
F-007 | 50 | 35 | 15 |
F-008 | 50 | 30 | 20 |
Materials | %w/w | ||
---|---|---|---|
F2 | F4 | F6 | |
Intragranular | |||
HME milled extrudates | 50.00 | 33.33 | 25.00 |
Avicel PH102 (microcrystalline cellulose) | 29.00 | 40.00 | 45.00 |
SuperTab 21AN (lactose anhydrous) | 14.00 | 19.67 | 23.00 |
Aerosil 200 (colloidal silicon dioxide) | 1.00 | 1.00 | 1.00 |
AC-DI-SOL (Croscarmellose sodium) | 3.00 | 3.00 | 3.00 |
Magnesium stearate | 0.50 | 0.50 | 0.50 |
Total Intragranular Portion | 97.50 | 97.50 | 97.50 |
Extragranular | |||
AC-DI-SOL (Croscarmellose sodium) | 2.00 | 2.00 | 2.00 |
Magnesium stearate | 0.50 | 0.50 | 0.50 |
Total Extragranular Portion | 2.50 | 2.50 | 2.50 |
Total | 100.00 | 100.00 | 100.00 |
Process Parameters | F1 | F2 | F3 | F4 | F5 | F6 | F7 | F8 |
---|---|---|---|---|---|---|---|---|
Zone 1 (C) | 25 | 25 | 25 | 25 | 25 | 25 | 25 | 25 |
Zone 2–8 (C) | 170 | 170 | 170 | 175 | 175 | 180 | 180 | upto 240 |
Die (C) | 165 | 165 | 165 | 170 | 170 | 175 | 175 | upto 235 |
Feed Rate (g/min) | 2.5–3.5 | 2.5–3.5 | 2.5–3.5 | 2.5–3.5 | 2.5–3.5 | 2.5–3.5 | 2.5–3.5 | 2.5–3.5 |
Screw Speed (RPM) | 50 | 50 | 50 | 50 | 50 | 50 | 50 | 50 |
Process torque (%) | 45–50 | 40–45 | 35–40 | 40–45 | 35–40 | 45–50 | 40–45 | 100 |
Die Nozzle (mm) | 2.5 | 2.5 | 2.5 | 2.5 | 2.5 | 2.5 | 2.5 | 2.5 |
Successful Extrusion (Yes/No) | Yes | Yes | Yes | Yes | Yes | Yes | Yes | No |
Formulation | Roll Force (kN) | Roll Speed (rpm) | Screw Speed (rpm) | Screw Current (Amps) | True Density (g/cm) | Envelop Density (g/cm) | Solid Fraction |
---|---|---|---|---|---|---|---|
F2 | 13 | 1 | 35–45 | 0.5–0.6 | 1.53 | 0.94 | 0.61 |
F4 | 13 | 1 | 30–35 | 0.35–0.45 | 1.54 | 1.12 | 0.73 |
F6 | 13 | 1 | 20–25 | 0.25–0.30 | 1.54 | 1.3 | 0.84 |
Formulation | Manufacturing Stage | Carr’s Index (%) | Hausner’s Ratio | Flow Function (FF) |
---|---|---|---|---|
F2 | HME Milled Powder | 36.45 (Very poor flow) | 1.49 | 2.45 (Poor flow) |
Pre-Roller Compaction Blend | 27.32 (Poor flow) | 1.37 | 5.66 (Intermediate flow) | |
Milled Ribbons | 18.36 (Fair flow) | 1.21 | 7.45 (Intermediate flow) | |
F4 | HME Milled Powder | 36.11 (Very poor flow) | 1.49 | 3.11 (Poor flow) |
Pre-Roller Compaction Blend | 22.51 (Passable flow) | 1.31 | 8.67 (Intermediate flow) | |
Milled Ribbons | 16.23 (Fair flow) | 1.22 | 12.08 (Good flow) | |
F6 | HME Milled Powder | 36.21 (Very poor flow) | 1.47 | 2.91 (Poor flow) |
Pre-Roller Compaction Blend | 19.32 (Fair flow) | 1.20 | 9.77 (Intermediate flow) | |
Milled Ribbons | 14.27 (Free flow) | 1.14 | 14.89 (Good flow) |
Formulation | Weight Variation (mg) | Thickness (mm) | Hardness (kp) | Friability (%) | Disintegration (s) | Assay (%) |
---|---|---|---|---|---|---|
F2 | 100.12 ± 0.72 | 2.49 ± 0.21 | 7.2 ± 1.7 | 0.43 | 180 | 98.23 ± 0.54 |
F4 | 99.23 ± 1.21 | 2.55 ± 0.12 | 7.3 ± 1.3 | 0.34 | 240 | 98.67 ± 0.34 |
F6 | 101.45 ± 1.67 | 2.63 ± 0.08 | 7.5 ± 0.9 | 0.41 | 270 | 99.31 ± 0.69 |
Stability Time Point | Formulation | Weight Variation (mg) | Hardness (kp) | Friability (%) | Disintegration (s) | Assay (%) |
---|---|---|---|---|---|---|
Initial (0 M) | F2 | 100.12 ± 0.72 | 7.2 ± 1.7 | 0.43 | 180 | 98.23 ± 0.54 |
F4 | 99.23 ± 1.21 | 7.3 ± 1.3 | 0.34 | 240 | 98.67 ± 0.34 | |
F6 | 101.45 ± 1.67 | 7.5 ± 0.9 | 0.41 | 270 | 99.31 ± 0.69 | |
3 M | F2 | 98.34 ± 1.21 | 6.8 ± 0.7 | 0.54 | 196 | 99.15 ± 1.23 |
F4 | 99.45 ± 0.67 | 7.2 ± 1.6 | 0.41 | 235 | 100.45 ± 0.67 | |
F6 | 100.33 ± 1.09 | 7.1 ± 1.1 | 0.45 | 260 | 97.63 ± 0.32 | |
6 M | F2 | 98.11 ± 0.11 | 6.4 ± 1.6 | 0.57 | 187 | 97.11 ± 1.31 |
F4 | 100.01 ± 0.47 | 6.8 ± 0.5 | 0.44 | 238 | 101.21 ± 0.87 | |
F6 | 99.65 ± 2.45 | 6.7 ± 1.2 | 0.41 | 265 | 100.09 ± 1.67 |
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© 2025 by the authors. Published by MDPI on behalf of the Österreichische Pharmazeutische Gesellschaft. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
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Vidiyala, N.; Sunkishala, P.; Parupathi, P.; Mandati, P.; Mantena, S.K.; Kasu, R.R.R.; Nyavanandi, D. High Drug Loading of Amorphous Solid Dispersion by Hot Melt Extrusion: The Role of Magnesium Aluminometasilicate (Neusilin® US2). Sci. Pharm. 2025, 93, 30. https://doi.org/10.3390/scipharm93030030
Vidiyala N, Sunkishala P, Parupathi P, Mandati P, Mantena SK, Kasu RRR, Nyavanandi D. High Drug Loading of Amorphous Solid Dispersion by Hot Melt Extrusion: The Role of Magnesium Aluminometasilicate (Neusilin® US2). Scientia Pharmaceutica. 2025; 93(3):30. https://doi.org/10.3390/scipharm93030030
Chicago/Turabian StyleVidiyala, Nithin, Pavani Sunkishala, Prashanth Parupathi, Preethi Mandati, Srujan Kumar Mantena, Raghu Rami Reddy Kasu, and Dinesh Nyavanandi. 2025. "High Drug Loading of Amorphous Solid Dispersion by Hot Melt Extrusion: The Role of Magnesium Aluminometasilicate (Neusilin® US2)" Scientia Pharmaceutica 93, no. 3: 30. https://doi.org/10.3390/scipharm93030030
APA StyleVidiyala, N., Sunkishala, P., Parupathi, P., Mandati, P., Mantena, S. K., Kasu, R. R. R., & Nyavanandi, D. (2025). High Drug Loading of Amorphous Solid Dispersion by Hot Melt Extrusion: The Role of Magnesium Aluminometasilicate (Neusilin® US2). Scientia Pharmaceutica, 93(3), 30. https://doi.org/10.3390/scipharm93030030