High-pressure high-temperature phase diagram of organic crystal paracetamol

At a Glance

Metadata	Details
Publication Date	2016-01-06
Journal	Journal of Physics Condensed Matter
Authors	Spencer J. Smith, Jeffrey Montgomery, Yogesh K. Vohra
Institutions	University of Alabama at Birmingham
Citations	9
Analysis	Full AI Review Included

Technical Documentation: High-Pressure High-Temperature Diamond Anvil Cell Components

Executive Summary

This study, utilizing high-pressure high-temperature (HPHT) Raman spectroscopy, demonstrates the critical role of specialized diamond components in advanced pharmaceutical research, specifically mapping the phase diagram of paracetamol.

Core Achievement: Generation of the first HPHT phase diagram for the organic crystal paracetamol, confirming complex polymorphism (Forms I, II, IV, V) under extreme conditions.
Enabling Technology: The experiment relied fundamentally on a Boron-Doped Designer Diamond Anvil (BDD) to provide direct, rapid, and controlled heating of the high-pressure specimen.
Pressure/Temperature Range: Data was acquired up to 8.5 GPa pressure and 520 K (247 °C) temperature, crucial ranges for simulating pharmaceutical processing stresses.
Phase Transitions Identified: Clear solid-state phase transitions (e.g., Form I→II, Form II→IV, Form IV→V) were inferred via abrupt shifts and discontinuities in Raman vibrational modes.
Future Development Opportunity: The research indicates a need for future experiments using two heating anvils to reduce temperature uncertainty, representing a direct requirement for dual BDD anvils.
Material Specification: The use of 500 µm culet diamond anvils highlights the need for precise geometry and doping uniformity available via 6CCVD’s MPCVD manufacturing process.

Technical Specifications

Parameter	Value	Unit	Context
Maximum Pressure Achieved	8.5	GPa	Isobaric measurement limit
Maximum Temperature Achieved	520	K	Highest observed melt transition point
Diamond Anvil Culet Size	500	µm	Used for high-pressure compression
Sample Chamber Diameter	~180	µm	Inconel Gasket hole size (pre-indented)
Initial Gasket Thickness	~100	µm	Pre-indented thickness
Sample Bulk Modulus	13	GPa	Indicates soft material, allowing quasi-hydrostatic conditions
Raman Excitation Wavelength	532	nm	Modulated green laser source
Form I → II Transition Boundary (3.8 GPa)	367	K	Solid state phase transition point
Persistence of Form II	6.9	GPa	Observed stability range (at 316 K)
Slope of Melt Line (dT/dP)	Positive	N/A	Indicates liquid phase has lower density

Key Methodologies

The HPHT phase mapping was conducted using specialized diamond anvil cell (DAC) technology integrated with Raman spectroscopy. The methodology centers on achieving precise, simultaneous control over pressure and high temperature.

Diamond Anvil Selection: A Boron-Doped Designer Diamond Anvil was utilized as the heating element due to its conductive properties, enabling direct and rapid heating of the high-pressure specimen.
Pressure Generation: A gas-membrane DAC was used to apply pressure via pressurized nitrogen (N₂). Pressure was measured dynamically using the shift of the ruby R₁ fluorescence line, corrected for temperature effects.
Thermal Management: The heating diamond’s temperature was measured via direct contact thermocouples. Sapphire support plates were used to thermally insulate the diamond anvils from the surrounding copper beryllium DAC body.
Pressure Medium/Insulator: Polycrystalline steatite was employed to surround the sample, acting as both a thermal insulator (from the non-heating diamond) and the pressure medium, ensuring quasi-hydrostatic conditions.
Raman Spectroscopy: A 532 nm laser was used to excite the sample. Phase transitions were identified by monitoring discontinuous frequency shifts, abrupt appearances, and disappearances of characteristic Raman peaks corresponding to different polymorphs.

6CCVD Solutions & Capabilities

6CCVD is uniquely positioned to supply the advanced MPCVD diamond materials necessary to replicate and extend this HPHT research into complex molecular crystals and pharmaceutical compounds. Our boron-doped (BDD) material is engineered specifically for high-pressure, high-temperature DAC applications.

Experimental Requirement	6CCVD Material/Capability	Value Proposition
Boron-Doped Heating Anvils	BDD Single Crystal Diamond (SCD)	We provide highly conductive, homogeneously doped SCD designed for resistive heating up to 1200 K, ensuring uniform sample temperature distribution.
Custom Culet Geometry (500 µm)	Custom Dimensions & Polishing	6CCVD fabricates SCD/PCD wafers up to 125mm and offers precise laser cutting and polishing (Ra < 1 nm for SCD) to meet exact culet and pavilion geometry requirements.
Advanced HPHT Research	Thick SCD & PCD Substrates	Our capability to grow thick substrates (up to 10 mm) allows for the creation of robust DAC components optimized for ultra-high-pressure applications (10+ GPa).
Integrated Temperature Sensing	Custom Metalization Services	Although the paper used external thermocouples, 6CCVD can deposit custom Ti/Pt/Au or W/Cu metal layers directly onto the diamond surface for integrated resistive heaters or thin-film thermocouple contacts, optimizing stability and responsiveness.
Future Dual-Heater Experiments	Matched Pair SCD BDD Anvils	We can supply precision-matched pairs of BDD anvils, essential for future work aiming to eliminate the temperature gradient uncertainty noted in the paper and establish precise triple points.
Thermal Insulation (Sapphire)	Alternative Dielectric Layers	While sapphire was used here, 6CCVD offers consultation on specialized thin-film dielectric coatings for enhanced thermal or electrical insulation within complex DAC setups.

Applicable Materials

To replicate and advance the HPHT study of pharmaceutical polymorphism, the following 6CCVD materials are recommended:

Electronic Grade Boron-Doped Single Crystal Diamond (BDD-SCD): Required for highly controlled and rapid resistive heating in the DAC configuration. Our SCD exhibits superior thermal stability and electrical homogeneity compared to non-custom materials.
Optical Grade Single Crystal Diamond (SCD): Recommended for the non-heating anvil to ensure high transparency (for the 532 nm Raman laser and pressure marker fluorescence) and mechanical integrity under maximum pressure (8.5+ GPa).

Customization Potential

The experiment’s success relied on a precisely fabricated BDD anvil with a 500 µm culet. 6CCVD specializes in providing diamond wafers and plates with:

Custom Geometric Machining: Precise culet sizes and orientations for specific pressure requirements (500 µm or smaller).
Metalization Schemes: Offering standard Au, Pt, Pd, Ti, W, and Cu metalization layers for integrated electrical contacts on BDD heaters, simplifying DAC assembly and improving reliability.

Engineering Support

6CCVD’s in-house team of PhD material scientists has extensive expertise in the integration of MPCVD diamond into high-pressure systems. We can assist researchers in material selection, thermal modeling, and BDD doping optimization for similar HPHT studies of molecular crystals and polymorphic pharmaceuticals.

For custom specifications or material consultation, visit 6ccvd.com or contact our engineering team directly.

View Original Abstract

High-pressure high-temperature (HPHT) Raman spectroscopy studies have been performed on the organic crystal paracetamol in a diamond anvil cell utilizing boron-doped heating diamond anvil. Isobaric measurements were conducted at pressures up to 8.5 GPa and temperature up to 520 K in five different experiments. Solid state phase transitions from monoclinic Form I → orthorhombic Form II were observed at various pressures and temperatures as well as transitions from Form II → unknown Form IV. The melting temperature for paracetamol was observed to increase with increasing pressures to 8.5 GPa. This new data is combined with previous ambient temperature high-pressure Raman and x-ray diffraction data to create the first HPHT phase diagram of paracetamol.

Tech Support

Original Source

DOI: https://doi.org/10.1088/0953-8984/28/3/035101