Chemometric evaluation of brompheniramine-tannate complexes

Area of Science:

• Analytical Chemistry
• Pharmaceutical Sciences
• Spectroscopy

Background:

• Brompheniramine (BP) tannate complexes are used for sustained drug delivery.
• Characterizing critical quality attributes (CQAs) of these complexes is crucial for ensuring product performance.
• Traditional methods for CQA assessment can be time-consuming and may not provide spatial information.

Purpose of the Study:

• To evaluate the efficacy of Raman and near-infrared (NIR) spectroscopy coupled with chemometrics for characterizing BP-tannate complexes.
• To assess the ability of these techniques to predict solubility, dissolution, and spatial distribution of BP within the complexes.
• To determine the variability in tannate complexation.

Main Methods:

• Seven BP-tannate complexes were prepared and analyzed using NIR chemical imaging (CI).
• Spectroscopic data (Raman and NIR) were pretreated and analyzed using Principal Component Analysis (PCA).
• Partial Least Squares Regression (PLSR) and Principal Component Regression (PCR) models were developed to predict CQAs.

Main Results:

• Fourier Transform Infrared (FTIR) analysis confirmed complexation, leading to reduced solubility and sustained release in alkaline media.
• NIR spectroscopy demonstrated superior discrimination ability compared to Raman spectroscopy.
• PLSR models, particularly with second-derivative pretreatment, showed lower prediction errors for solubility and dissolution rates compared to PCR.
• NIR-CI models achieved high correlation (>0.95) for predicting drug concentration, validating spatial quantitation capabilities.

Conclusions:

• Chemometric analysis of NIR and/or Raman spectra offers an innovative and effective approach for determining tannate complexation variability.
• The combined spectroscopic and chemometric methods provide a robust platform for characterizing CQAs of pharmaceutical complexes.
• NIR-CI, in particular, is validated for the spatial quantitation of active pharmaceutical ingredients within complexes.