Applications of terahertz spectroscopy to pharmaceutical sciences

Area of Science:

• Pharmaceutical analysis
• Spectroscopy
• Process Analytical Technology (PAT)

Background:

• Pharmaceutical manufacturing requires rigorous quality control to ensure drug efficacy and safety.
• Changes in active pharmaceutical ingredients' solid-state form can impact drug performance.
• Process Analytical Technology (PAT) initiatives aim to improve manufacturing processes through real-time monitoring.

Purpose of the Study:

• To evaluate the application of terahertz pulsed spectroscopy (TPS) for quantitative analysis of pharmaceutical ingredients.
• To demonstrate TPS's utility within the FDA's PAT initiative.
• To assess the accuracy of TPS in determining potency levels and excipient information in tablets.

Main Methods:

• Terahertz absorption spectra of test tablets containing paracetamol and aspirin were acquired.
• Multivariate partial-least-squares (PLS) calibration models were developed.
• Root-mean-square errors of cross-validation (RMSECVs) were calculated to assess model accuracy.

Main Results:

• Accurate potency levels for paracetamol (RMSECV 2.85%) and aspirin (RMSECV 3.90%) were recovered.
• Excipient information, specifically lactose content, was also successfully quantified (RMSECVs 3.65% and 4.30%).
• The study highlights the potential for real-time monitoring of pharmaceutical ingredients.

Conclusions:

• Terahertz pulsed spectroscopy is a viable high-throughput technique for pharmaceutical quality control.
• TPS can monitor active ingredients and excipients, supporting a 'right-first-time' manufacturing approach.
• The findings support the integration of TPS into PAT strategies for enhanced pharmaceutical production.