Here’s a comprehensive, training-ready module on Collecting Fractions in Supercritical CO₂ Extraction (SFE), designed for lab, pilot, and industrial settings, integrating selectivity, QbD, and GMP principles.
Objective: Efficiently separate and collect distinct chemical fractions to maximize purity, value, and reproducibility.
1. Why Fraction Collection Matters
- Enhances selectivity: separate light volatiles from heavier compounds
- Improves product value: premium fractions (aromas, actives) are isolated
- Facilitates analytical characterization: fraction-resolved profiling
- Supports GMP compliance: traceable batch documentation
Fraction collection transforms SFE from a single “bulk extract” process into a high-resolution separation tool.
2. Types of Fractions
| Fraction Type | Typical Setting | Compounds Captured |
|---|---|---|
| F1 – Light volatiles | Low P / low T | Monoterpenes, light aromatics |
| F2 – Medium | Moderate P / T | Sesquiterpenes, mid-weight compounds |
| F3 – Heavy | High P / higher T | Chromones, waxes, resins |
| Optional F4 | Very high P / T | Residual heavy compounds |
📌 Number of fractions depends on:
- Target compounds
- Scale of extraction
- Downstream application
3. Fraction Collection Hardware
- Primary separator: separates CO₂ from dissolved compounds
- Secondary separator(s): optional for multi-step fractionation
- Pressure/temperature control: adjust P/T to selectively precipitate compounds
- Collection vessels: glass, stainless steel, or PTFE, compatible with intended product
4. Key Fractionation Principles
A. Pressure Drop
- Lowering pressure causes solutes to precipitate
- Stepwise depressurization allows sequential recovery of fractions
B. Temperature Control
- Separators often heated/cooled to stabilize solutes
- Light volatiles condense at lower temperatures
- Heavy resins require moderate heating to remain fluid for collection
C. Modifier Effects
- Co-solvent presence alters solubility
- Adjust separator conditions if modifier used
D. Residence Time
- Adequate CO₂ contact in separator ensures complete precipitation
5. Step-by-Step Fraction Collection
- Activate primary separator at target P/T
- Direct CO₂ stream through separator
- Collect precipitated fraction in pre-weighed vessel
- Adjust P/T for next fraction
- Repeat for each stage until extraction complete
- Record fraction mass, P/T conditions, CO₂ usage
- Store fractions appropriately (cold, dark, inert atmosphere if required)
6. Documentation & Traceability
For each fraction, record:
| Parameter | Example |
|---|---|
| Fraction ID | F1, F2, F3 |
| Batch ID | LAB-001 |
| Mass collected | 2.34 g |
| Separator P/T | 100 bar / 35 °C |
| CO₂ usage | 12 kg/kg feed |
| Time | 30 min |
| Notes | Appearance, color, odor |
📌 Fraction metadata is critical for QbD and GMP reporting
7. Common Fraction Collection Mistakes
- Inconsistent P/T → overlapping fractions
- Vessel under- or overfilled → loss or contamination
- No labeling → fraction mix-up
- Ignoring modifier carryover → altered composition
- Rapid depressurization → foaming or CO₂ loss
8. Best Practices
- Pre-weigh collection vessels
- Minimize headspace for volatile fractions
- Use inert gas (N₂) to prevent oxidation if needed
- Cool sensitive fractions immediately
- Maintain data log of P/T/CO₂ for each fraction
9. Analytical Considerations
- Analyze each fraction separately (GC-MS, HPLC, LC-MS)
- Determine target compound concentration in each fraction
- Use results to adjust future runs for optimal selectivity
10. Key Takeaways
Fractions are the value centers in SFE.
- Plan fractions based on target compounds & application
- Use controlled P/T adjustment to precipitate selectively
- Record full metadata for reproducibility
- Analyze fractions individually to guide process optimization
I can also create a visual fractionation map with recommended P/T ranges and compound classes for perfumery, nutraceuticals, and pharmaceuticals, which is ideal for training slides or SOPs.
Do you want me to make that next?