Raman

Raman Spectroscopy for Pharmaceutical

Raman spectroscopy plays a crucial role in the pharmaceutical industry by addressing key needs such as drug purity, authenticity, and efficacy. Indeed, this technique is used to verify raw materials, detect counterfeit drugs, monitor polymorphic forms, and analyze drug formulations.

It requires minimal sample preparation and provides precise molecular identification and characterization. By offering real-time, in-line monitoring and detailed spatial distribution information, Raman spectroscopy enhances quality control, supports regulatory compliance, accelerates drug development, and effectively meets the industry's challenges in maintaining high standards and safeguarding public health.

Raman spectroscopy for Pharmaceutical Processes

The Challenges of Pharmaceutical for Raman Spectroscopy

Understanding the polymorphs of Active Pharmaceutical Ingredients (API)

Different polymorphic forms of an API can have varying properties like solubility, stability, and bioavailability, which affect the drug's performance, safety, and shelf life.

Identifying and controlling the specific polymorph used in a pharmaceutical product ensures consistent performance, efficacy, and regulatory compliance, ultimately protecting patient health and enhancing the drug's therapeutic effectiveness. This can be done with Raman spectroscopy.

In drug discovery and drug development, Raman spectroscopy is used to:

Differentiate between polymorphs by analyzing their unique Raman spectra.
Quantify the proportions of different polymorphs in a mixture by analyzing the intensity ratios of specific Raman peaks corresponding to each polymorph.
Predict shelf-life and the stability of the polymorphs by monitoring the Raman spectra of the samples treated in different environments (e.g. temperature, humidity).

Raman spectroscopy for Pharmaceutical - Polymorphisms

Low frequency Raman spectra of Carbamazepine grains of powder. Form I: High solubility. Form III: low solubility. (App. note HORIBA RA75)

Monitoring the distribution of compounds during formulation

The uniform distribution of the active pharmaceutical ingredient (API) and excipients guarantees that each dose contains the correct amount of medication, providing the intended therapeutic effect.

Ensuring even distribution is critical for meeting quality standards, maintaining regulatory compliance, and safeguarding patient health by delivering a safe and effective product.

Drug development uses Raman Spectroscopy to:

Analyze the uniformity of distribution of different compounds within a formulation by mapping the spatial distribution of different components within a tablet or other dosage forms.
Monitor the distribution of compounds in real-time during the formulation process. By integrating Raman spectroscopy in an in-line manufacturing process, it is possible to adjust the formulation process on-the-fly to ensure uniformity and quality.

Raman spectroscopy for Pharmaceutical - Compounds Distribution

8-vitamins tablet Raman mapping. Left: MCR spectra identified by the database. Right: Chemical distribution based on MCR decomposition. Scale bar: 200 μm. (App. note HORIBA RA78)

Characterizing defects and outliers on final products

Characterizing defects and outliers in final pharmaceutical products is necessary to ensure the quality, safety, and efficacy of the medication. Identifying defects prevents compromised products from reaching patients.

By detecting and addressing outliers, manufacturers can maintain consistency across batches, adhere to regulatory standards, and uphold the integrity of their brand. Therefore, Raman Spectroscopy is used in Manufacturing and Post-marketing surveillance to:

Analyze the surface of final products to identify defects such as cracks, inclusions, improper crystallization or contamination up to microscopic size thanks to its high spatial resolution.
Identify and analyze outliers, helping to understand their origin and prevent future occurrences by providing detailed information on the chemical composition of the material.
Ensure consistency of batches by comparing spectra of products.
Investigate the cause of defects by analyzing the molecular structure and composition of the impacted regions.

Raman spectroscopy for Pharmaceutical - Contamination

Example of non-compliance of pharmaceutical tablets because of presence of contamination

Evolving in a highly regulated environment

The pharmaceutical industry is highly regulated, with stringent documentation requirements to ensure the safety and efficacy of products.

Raman spectroscopy is an essential tool in this landscape, offering non-destructive analysis that provides detailed insights into their chemical composition and molecular structure. This technique is crucial for quality control, allowing for the rapid identification and verification of raw materials, active pharmaceutical ingredients (APIs), and finished products, ensuring they meet the rigorous standards set by regulatory bodies.

In both laboratory quality control and production settings, Raman spectroscopy plays a key role in maintaining product integrity:

Provide immediate and accurate data on the chemical properties of materials, aiding in the detection of impurities or deviations from the expected composition. This ensures that each batch of a product is consistent and safe for use.
Support compliance with regulatory requirements like CFR 21 Part 11, which mandates secure and traceable electronic records. By aligning with these regulations, Raman spectroscopy enhances quality assurance and ensures that all data is accurately recorded and readily available for audits, supporting compliance with pharmacopeial standards (e.g., USP, EP) and other regulatory frameworks.

>> Explore our solutions for Raman analysis <<