Drug characterization in low dosage pharmaceutical tablets using Raman microscopic mapping.

Area of Science:

• Pharmaceutical analysis
• Solid-state chemistry
• Materials science

Background:

• Pharmaceutical tablets often contain low concentrations of active pharmaceutical ingredients (APIs).
• Understanding API spatial distribution and polymorphic form is crucial for drug product quality and efficacy.
• Traditional methods may struggle to analyze low-dosage APIs within complex tablet matrices.

Purpose of the Study:

• To investigate the utility of Raman micro-spectroscopic mapping for analyzing low-dosage APIs in pharmaceutical tablets.
• To assess the capability of Raman mapping in determining API domain size, spatial distribution, and polymorphic purity.
• To evaluate the potential of this technique for quality control and process optimization in pharmaceutical manufacturing.

Main Methods:

• Raman micro-spectroscopic mapping was employed to analyze pharmaceutical tablets with 0.5% w/w API.
• Domain sizes and spatial distributions of API and excipients were determined.
• Multivariate classification was used to identify undesired API polymorphs.

Main Results:

• API domain size correlated with the particle size distribution of the source API material.
• Raman maps effectively indicated the origin of the API used in tablet production.
• The technique detected as little as 10% form conversion of the low-dosage API, equivalent to 0.05% w/w polymorphic impurity.

Conclusions:

• Raman micro-spectroscopic mapping provides valuable insights into API characteristics within tablets.
• The method is sensitive enough for detecting low-level polymorphic impurities.
• This technique holds potential for optimizing pharmaceutical manufacturing processes and predictive stability assessments.