Liquid–liquid equilibrium measurements and computational study of salt–polymer aqueous two phase system for extraction of analgesic drugs
At a Glance
Section titled “At a Glance”| Metadata | Details |
|---|---|
| Publication Date | 2022-08-16 |
| Journal | Scientific Reports |
| Authors | Fariba Ghaffari, Mohammad Khorsandi, Hemayat Shekaari, Mohammed Taghi Zafarani-Moattar |
| Institutions | University of Tabriz |
| Citations | 12 |
| Analysis | Full AI Review Included |
Executive Summary
Section titled “Executive Summary”This research successfully characterized an Aqueous Two-Phase System (ATPS) composed of Polyethylene Glycol 600 (PEG600) and Potassium Hydroxide (KOH) for the efficient extraction of analgesic drugs (Ibuprofen and Acetaminophen).
- High Extraction Efficiency: The system achieved high extraction efficiencies (EE%) for both drugs, peaking at 93.42% for Ibuprofen and 92.30% for Acetaminophen, demonstrating strong potential for pharmaceutical separation.
- Hydrophobicity Driven Separation: Partitioning coefficients (K) confirmed that extraction into the polymer-rich (top) phase is primarily driven by the drug’s hydrophobicity (Ibuprofen > Acetaminophen).
- LLE Modeling: Experimental Liquid-Liquid Equilibrium (LLE) data, including binodal curves and tie-lines, were accurately correlated using established semi-empirical equations (Merchuk, Zafarani-Moattar, Othmer-Tobias, Bancraft, Setschenow).
- Advanced Computational Validation: Density Functional Theory (DFT), Quantum Theory of Atoms in Molecules (QTAIM), and Natural Bond Orbital (NBO) analyses were used to confirm intermolecular interactions, showing that Ibuprofen-PEG interactions were structurally more stable than Acetaminophen-PEG.
- Relevance to 6CCVD: The analytical methods employed (spectroscopy, high-precision mass measurement) and the application (pharmaceutical separation) are highly relevant to advanced analytical platforms utilizing high-purity MPCVD diamond for sensing and optical components.
Technical Specifications
Section titled “Technical Specifications”The following hard data points were extracted from the experimental and computational sections of the paper:
| Parameter | Value | Unit | Context |
|---|---|---|---|
| System Temperature | 298.15 | K | LLE and ATPS measurements |
| System Pressure | ≈ 85 | kPa | Atmospheric pressure during experiments |
| PEG Molar Mass | 600 | g mol-1 | Polyethylene Glycol (PEG600) used |
| Maximum Ibuprofen EE% | 93.42 | % | Achieved at highest Tie-Line Length (TLL) |
| Maximum Acetaminophen EE% | 92.30 | % | Achieved at highest TLL |
| Ibuprofen log Kow | 3.97 | - | Hydrophobicity indicator |
| Acetaminophen log Kow | 2.34 | - | Hydrophobicity indicator |
| Refractive Index Precision | ± 0.0001 | - | Used for PEG concentration determination |
| Analytical Balance Precision | ± 1.10-7 | kg | Used for mass fraction determination |
| Ibuprofen-PEG Interaction Energy (ΔEint) | -9.63 | kcal/mol | WB97xd functional calculation |
| Acetaminophen-PEG Interaction Energy (ΔEint) | -16.90 | kcal/mol | WB97xd functional calculation |
| Strongest NBO Interaction (Ibuprofen-PEG E2) | 16.12 | kcal/mol | LP(O) to BD*(O-H) transfer |
Key Methodologies
Section titled “Key Methodologies”The study utilized a combination of precise physical chemistry techniques and advanced quantum computing methods:
- Phase Diagram Determination:
- Cloud point titration method was used to determine the binodal curves at 298.15 K and 85 kPa.
- Aqueous solutions of PEG600 (60 wt%) and KOH (50 wt%) were used.
- Tie-Line Determination:
- Five different mixture compositions were gravimetrically prepared and vigorously stirred for 30 minutes, followed by centrifugation and equilibrium in a water bath (298 K).
- KOH concentration was determined by flame photometer.
- PEG concentration was determined by refractive index measurements (precision ± 0.0001).
- Drug Partitioning Analysis:
- Ibuprofen and Acetaminophen were added (0.002 mass fraction) to the equilibrated ATPS mixtures.
- Drug concentrations in the separated phases were determined using UV spectrophotometry (Acetaminophen) and fluorescence spectrophotometry (Ibuprofen).
- Computational Modeling (DFT):
- Geometry optimization and energetic parameters were calculated using Density Functional Theory (DFT) with B3LYP-D3(BJ), M06-2x, and WB97X-D3 functionals.
- QTAIM (Quantum Theory of Atoms in Molecules): Used to characterize critical points (atom, bond, ring, cage) and analyze the nature of intermolecular interactions (ionic-covalent vs. Van der Waals).
- NBO (Natural Bond Orbital): Used to calculate donor-acceptor interactions and Wiberg bond indices (WBI) to quantify H-bond strength.
- RDG (Reduced Density Gradient): Used for visualizing and evaluating noncovalent interactions in real space.
6CCVD Solutions & Capabilities
Section titled “6CCVD Solutions & Capabilities”This research highlights the critical need for high-precision analytical tools—specifically high-sensitivity spectroscopy and potential electrochemical analysis—to monitor complex chemical separations in pharmaceutical applications. 6CCVD provides the advanced MPCVD diamond materials necessary to build next-generation analytical systems that replicate or extend this work.
Applicable Materials
Section titled “Applicable Materials”| Research Requirement | 6CCVD Material Solution | Key Benefit |
|---|---|---|
| High-Precision Optical Measurement (Refractometry, UV/Fluorescence Spectroscopy) | Optical Grade Single Crystal Diamond (SCD) | Ultra-wide transparency range (UV to Far-IR), high thermal conductivity, and chemical inertness, ideal for high-power or corrosive ATPS environments. Polishing available to Ra < 1nm. |
| Electrochemical Sensing/Monitoring (Future Extension of Drug Analysis) | Heavy Boron-Doped Diamond (BDD) | Superior electrode material for analyzing Ibuprofen and Acetaminophen due to wide potential window, low background current, and exceptional stability in harsh chemical matrices (like KOH/PEG). |
| Large-Area Separation Platforms (Microfluidics, Flow Cells) | Polycrystalline Diamond (PCD) Wafers | Custom dimensions up to 125mm, providing robust, chemically inert substrates for integrating microfluidic channels or sensor arrays for continuous ATPS monitoring. |
Customization Potential
Section titled “Customization Potential”The integration of advanced separation techniques, such as the ATPS studied here, into industrial or laboratory settings often requires highly customized components. 6CCVD specializes in meeting these unique engineering demands:
- Custom Dimensions and Thickness: We provide SCD and PCD plates/wafers in custom sizes up to 125mm (PCD) and thicknesses ranging from 0.1µm to 500µm, allowing for precise integration into custom flow cells or spectrophotometer windows.
- Precision Polishing: Our internal polishing capabilities ensure surfaces suitable for high-resolution optical and sensing applications (Ra < 1nm for SCD, Ra < 5nm for inch-size PCD).
- Integrated Metalization: For creating integrated sensor arrays or electrical contacts required for BDD electrodes, 6CCVD offers in-house metalization services, including Au, Pt, Pd, Ti, W, and Cu layers, tailored to specific device architectures.
Engineering Support
Section titled “Engineering Support”The successful application of ATPS for drug separation relies on understanding complex chemical interactions, as demonstrated by the extensive DFT and QTAIM analysis in this paper. 6CCVD’s in-house PhD team offers expert material consultation to assist engineers and scientists in selecting and designing diamond components for similar Pharmaceutical Separation and Advanced Chemical Analysis projects. We ensure the optimal diamond grade (SCD, PCD, or BDD) and surface preparation are chosen to maximize analytical performance and system longevity.
For custom specifications or material consultation, visit 6ccvd.com or contact our engineering team directly.