SEDEX—Self-Emulsifying Delivery Via Hot Melt Extrusion: A Continuous Pilot-Scale Feasibility Study
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Liquid SEDDS Preparation and Polymer Solubility
2.3. Drying of Polymers
2.4. Oil-Binding Capacity
2.5. Hot Melt Extrusion
2.6. HME–SEDDSs Characterization
2.6.1. Polarized Optical Microscopy (POM)
2.6.2. Differential Scanning Calorimetry (DSC)
2.6.3. Wide-Angle X-ray Scattering (WAXS)
2.6.4. Emulsification Time
2.6.5. Droplet Size and Polydispersity Index (PDI)
2.6.6. Transmittance and Cloud Point
3. Results and Discussion
3.1. Oil-Binding Capacity
3.2. Hot Melt Extrusion (HME)
3.3. HME–SEDDSs Characterization
3.3.1. Polarized Optical Microscopy (POM)
3.3.2. Thermal Phase Behavior of HME–SEDDSs Formulations
3.3.3. Crystallinity of HME–SEDDSs Observed Via WAXS
3.3.4. Trends in Emulsification Efficiency among HME–SEDDSs Formulations
3.3.5. Droplet Size and Polydispersity Index (PDI) Obtained from HME–SEDDSs
3.3.6. Transmittance and Cloud Point
4. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
ASD | Amorphous solid dispersion |
DSC | Differential scanning calorimetry |
GMP | Good manufacturing practice |
HME | Hot melt extrusion |
HME–SEDDS | Solid SEDDSs prepared by hot melt extrusion |
HPC | Hydroxy propyl cellulose |
HPMCAS | Hydroxy propyl methylcellulose-acetate/succinate |
LOD | Loss on drying |
MCC | Microcrystalline cellulose |
PAT | Process analytical technology |
PDI | Polydispersity index |
PL_630 | Plasdone® 630 |
PL_630_U | Plasdone® 630 Ultra |
SEDDSs | Self-emulsifying drug delivery systems |
SEDEXSOL | Self-emulsifying delivery via extrusionSoluplus® |
SOL-HME–SEDDSs | Solid SEDDSs prepared by hot melt extrusion with Soluplus® |
VA-64 | Kollidon® VA-64, copovidone |
VA-64-HME–SEDDSs | Solid SEDDSs prepared by hot melt extrusion with Kollidon VA-64® |
WAXS | Wide-angle X-ray scattering |
ZSK18 | Co-rotating closely intermeshing twin screw extruder from Coperion with a nominal screw diameter of 18 mm |
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Formulation | Composition |
---|---|
Liquid SEDDSs | 30% Labrafac® lipophile 30% Kolliphor® RH40 30% Capmul® MCM 10% Transcutol® |
HME–SEDDSs 10% BLANK | 90% Polymer * 3% Labrafac® lipophile 3% Kolliphor® RH40 3% Capmul® MCM 1% Transcutol® |
HME–SEDDSs 20% BLANK | 80% Polymer * 6% Labrafac® lipophile 6% Kolliphor® RH40 6% Capmul® MCM 2% Transcutol® |
HME–SEDDSs 30% BLANK | 70% Polymer * 9% Labrafac® lipophile 9% Kolliphor® RH40 9% Capmul® MCM 1% Transcutol® |
Concentration | 0.4% w/v | 2.0% w/v | ||||||
---|---|---|---|---|---|---|---|---|
Temperature | 25 °C | 37 °C | 25 °C | 37 °C | ||||
Droplet Size (nm) | PDI | Droplet Size (nm) | PDI | Droplet Size (nm) | PDI | Droplet Size (nm) | PDI | |
Blank SEDDSs | 31.8 | 0.051 | 35.8 | 0.035 | 32.5 | 0.048 | 36.0 | 0.041 |
HME–SEDDSs–10%–VA-64 | 122.7 | 0.214 | 136.1 | 0.197 | 257.1 | 0.255 | 286.0 | 0.256 |
HME–SEDDSs–20%–VA-64 | 152.9 | 0.193 | 170.6 | 0.132 | 259.1 | 0.246 | 234.4 | 0.269 |
HME–SEDDSs–30%–VA-64 | 115.7 | 0.251 | 129.2 | 0.244 | 226.3 | 0.279 | 285.8 | 0.271 |
HME–SEDDSs–10%–SOL | 61.8 | 0.061 | 90.2 | 0.089 | 63.9 | 0.047 | 139.1 | 0.152 |
HME–SEDDSs–20%–SOL | 68.7 | 0.100 | 95.8 | 0.085 | 71.7 | 0.145 | 150.4 | 0.194 |
HME–SEDDSs–30%–SOL | 73.5 | 0.128 | 95.1 | 0.119 | 120.1 | 0.264 | 145.8 | 0.182 |
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Zupančič, O.; Doğan, A.; Matić, J.; Kushwah, V.; Alva, C.; Spoerk, M.; Paudel, A. SEDEX—Self-Emulsifying Delivery Via Hot Melt Extrusion: A Continuous Pilot-Scale Feasibility Study. Pharmaceutics 2022, 14, 2617. https://doi.org/10.3390/pharmaceutics14122617
Zupančič O, Doğan A, Matić J, Kushwah V, Alva C, Spoerk M, Paudel A. SEDEX—Self-Emulsifying Delivery Via Hot Melt Extrusion: A Continuous Pilot-Scale Feasibility Study. Pharmaceutics. 2022; 14(12):2617. https://doi.org/10.3390/pharmaceutics14122617
Chicago/Turabian StyleZupančič, Ožbej, Aygün Doğan, Josip Matić, Varun Kushwah, Carolina Alva, Martin Spoerk, and Amrit Paudel. 2022. "SEDEX—Self-Emulsifying Delivery Via Hot Melt Extrusion: A Continuous Pilot-Scale Feasibility Study" Pharmaceutics 14, no. 12: 2617. https://doi.org/10.3390/pharmaceutics14122617
APA StyleZupančič, O., Doğan, A., Matić, J., Kushwah, V., Alva, C., Spoerk, M., & Paudel, A. (2022). SEDEX—Self-Emulsifying Delivery Via Hot Melt Extrusion: A Continuous Pilot-Scale Feasibility Study. Pharmaceutics, 14(12), 2617. https://doi.org/10.3390/pharmaceutics14122617