During active pharmaceutical ingredient (API) crystallization and drying, comprehensive process understanding demands simultaneous insight into chemical composition and solid-state structure. Operators routinely track two distinct parameters in real time: residual solvent or moisture content, and crystal polymorphism.
Historically, monitoring both attributes in situ presented a practical instrumentation bottleneck. Near-infrared (NIR) spectroscopy excels at quantifying water and solvent levels, while Raman spectroscopy provides the molecular fingerprint required to distinguish between polymorphic forms, hydrates, and amorphous phases. Running both techniques concurrently typically required two dedicated immersion probes—demanding multiple reactor ports that are rarely available on benchtop vessels, filter dryers, or pilot equipment.
Synchronous In Situ Acquisition in One Shaft
To solve this physical constraint, art photonics designed the NIRaman Combi Probe. By integrating a NIR diffuse-reflectance channel and a 785 nm Raman optical channel within a single 19 mm diameter shaft, the probe delivers synchronized measurements from the exact same sample volume.
Both channels collect spectral data concurrently without optical cross-talk, operating across powders, crystalline slurries, and liquid phases. Because measurements take place directly inside the process stream, the probe eliminates the need for sample extraction, bypass loops, or manual preparation.
Primary Application Areas
- API Crystallization & Drying: Real-time quantification of solvent removal kinetics via NIR paired with continuous verification of crystal structure and polymorphic purity via Raman.
- Raw Material Verification: Fast chemical identification and solid-state validation of incoming materials in a single measurement cycle.
- Blend Uniformity & Potency: Simultaneous tracking of active ingredient distribution and moisture balance during solid-dose blending.
- Reaction Kinetics & Phase Transitions: Continuous monitoring of reaction progress and intermediate phase formations from laboratory synthesis to commercial production.
From End-Product Testing to Active Process Control
Offline sampling and release testing only identify failures after the batch is completed. Detecting polymorphic shifts, unwanted solvate formations, or over-drying at the moment they occur allows operators to intervene immediately and steer the process within its validated design space.
The NIRaman Combi Probe is available in laboratory and pharma-grade configurations, featuring sanitary process connections and materials designed to meet pharmaceutical manufacturing standards.
