A New Control Strategy for High-Pressure Homogenization to Improve the Safety of Injectable Lipid Emulsions
Abstract
:1. Introduction
2. Materials and Methods
2.1. Lipofundin MCT/LCT 20%
2.2. Emulsification Process
2.3. Analytical Methods for Emulsion Characterization
2.3.1. Photon Correlation Spectroscopy
2.3.2. Single-Particle Optical Sensing
2.3.3. Optical Microscopy
2.3.4. Data Analysis
3. Results and Discussion
3.1. Effect of the Homogenization Cycles
3.2. Effect of Temperature and Pressure
3.3. Derived Control Strategy
4. Conclusions
5. Patents
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Raw Material | Amount | Supplier |
---|---|---|
Glycerol | 250.0 g | August Hedinger |
Egg lecithin | 120.0 g | Lipoid |
Sodium oleate | 3.0 g | Sigma-Aldrich Chemie |
Alpha-tocopherol | 2.0 g | Brenntag |
Refined Soybean Oil IV | 1000.0 g | Gustav Heess |
Medium chain triglyceride | 1000.0 g | Cremer Oleo |
Water for injection | 7625.0 g | B. Braun Melsungen |
Measurement Parameter | Setting |
---|---|
Light source | He-Nelaser (632.8 nm) |
Angle | 90° (singe angle analysis) |
Channel width | Automatic (20–30 µs) |
Temperature | 23 °C |
Viscosity (continuous phase) | 0.933 cP (water at 23 °C) |
Refractive index (continuous phase) | 1.333 (water) |
Measurement time | 10 min |
Number of measurements | 1 |
Measurement Parameter | Setting |
---|---|
Data Collection Time | 90 s |
Number of Channels | 128 |
Diluent Flow Rate | 60 mL/min |
Target Concentration | 1000 Part/mL |
Injection Loop Volume | 1.0 mL |
Syringe Volume | 2.5 mL |
Initial 2nd-Stage Dilution Factor | 100 |
Temperature [°C] | MPD [nm] Cycle 1: 1900 Bar Cycle 2: 500 Bar | MPD [nm] Cycle 1: 1500 Bar Cycle 2: 500 Bar | MPD [nm] Cycle 1: 1000 Bar Cycle 2: 500 Bar | MPD [nm] Cycle 1: 500 Bar Cycle 2: 500 Bar |
---|---|---|---|---|
20 | 273.7 ± 27.1 | 275.6 ± 89.6 | 332.6 ± 98.1 | 353.9 ± 167.7 |
30 | 264.6 ± 52.9 | 270.2 ± 7.8 | 303.5 ± 27.0 | 363.4 ± 102.5 |
40 | 265.2 ± 52.0 | 268.9 ± 42.8 | 305.7 ± 87.1 | 338.8 ± 72.8 |
50 | 255.1 ± 42.9 | 253.8 ± 47.0 | 281.8 ± 78.3 | 313.9 ± 99.8 |
60 | 229.4 ±48.9 | 256.0 ± 14.6 | 267.0 ± 23.0 | 298.5 ± 102.4 |
70 | 237.8 ± 63.0 | 251.0 ± 16.3 | 264.8 ± 33.6 | 290.5 ± 50.3 |
Cycle | Pressure | Temperature |
---|---|---|
primary | 500–1900 bar | 30–60 °C |
secondary | 500 bar | 30–60 °C |
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Grumbach, C.; Krüger, V.; Czermak, P. A New Control Strategy for High-Pressure Homogenization to Improve the Safety of Injectable Lipid Emulsions. Pharmaceutics 2022, 14, 1603. https://doi.org/10.3390/pharmaceutics14081603
Grumbach C, Krüger V, Czermak P. A New Control Strategy for High-Pressure Homogenization to Improve the Safety of Injectable Lipid Emulsions. Pharmaceutics. 2022; 14(8):1603. https://doi.org/10.3390/pharmaceutics14081603
Chicago/Turabian StyleGrumbach, Carsten, Volker Krüger, and Peter Czermak. 2022. "A New Control Strategy for High-Pressure Homogenization to Improve the Safety of Injectable Lipid Emulsions" Pharmaceutics 14, no. 8: 1603. https://doi.org/10.3390/pharmaceutics14081603
APA StyleGrumbach, C., Krüger, V., & Czermak, P. (2022). A New Control Strategy for High-Pressure Homogenization to Improve the Safety of Injectable Lipid Emulsions. Pharmaceutics, 14(8), 1603. https://doi.org/10.3390/pharmaceutics14081603