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Moisture Assessment of Freeze-Dried Biologics by Frequency Modulation Spectroscopy (FMS) (CAT#: STEM-ST-1616-CJ)

Introduction

Residual moisture is a critical quality attribute (CQA) for lyophilized biopharmaceutical drug products (DP) as it can impact the stability.1 Moisture content needs to be monitored closely during development, scale-up and process validation of a lyophilization cycle.




Principle

FM spectroscopy is an optical heterodyne detection, a signal of interest at some frequency is nonlinearly mixed with a reference "local oscillator" (LO) that is set at a close-by frequency. The desired outcome is the difference frequency, which carries the information of the original higher frequency signal, but is oscillating at a lower more easily processed carrier frequency. FM spectroscopy is a fast time response. When modulated light passes through absorbing sample, different components are absorbed. The exit laser light shows frequency modulation and little bit of angle modulation. Absorption transforms frequency modulation into amplitude modulation. Generated photo diode signal shows DC and superimposed AC current and AC component is demodulated using demodulation techniques. FM signal produced finally is proportional to concentration of detected species.

Applications

Biochemistry; Biopharmaceuticals; Pharmaceuticals

Procedure

1. Develop relevant parameter standards.
2. Preparation of drug samples.
3. Set up frequency modulation spectrum (FMS) device
4. Collect and analyze data.

Materials

• Sample: Placebo tablets (comprising microcrystalline cellulose, lactose, and magnesium stearate); Gelatin-encapsulated dry product (comprising proprietary drug, sucrose, microcrystalline cellulose, hydroxypropyl cellulose, and sodium lauryl sulfate); Lyophilized product (comprising proprietary drug, gelatin, mannitol, and citric acid); Desiccant; Liquid-filled hard gelatin capsule (proprietary drug and lipids) & More.
• Equipment: Frequency Modulation Spectroscopy (FMS) Analyzer.

Notes

1. FMS can be used as an ultra-high precision-frequency reference in the atom sensors.
2. Frequency-modulation spectroscopy is a powerful tool that can achieve high sensitivities with a relatively simple experimental setup.
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