Chemometric methods for the quantification of crystalline tacrolimus in solid dispersion by powder X-ray...

Area of Science:

• Pharmaceutical Sciences
• Analytical Chemistry
• Materials Science

Background:

• Solid dispersions (SDs) are crucial for improving drug solubility and bioavailability.
• Quantifying crystalline drug content in SDs is essential for quality control and predicting therapeutic efficacy.
• Powder X-ray diffraction (XRPD) is a powerful technique for characterizing crystalline materials.

Purpose of the Study:

• To develop a quantitative powder X-ray diffraction (XRPD) chemometric model for determining crystalline tacrolimus content in solid dispersions (SD).
• To establish a reliable quality control method for assessing the crystalline state of tacrolimus within pharmaceutical formulations.

Main Methods:

• Preparation of solid dispersions (SDs) with varying tacrolimus concentrations and mixtures of amorphous and crystalline tacrolimus.
• Utilizing powder X-ray diffraction (XRPD) to identify and quantify crystalline tacrolimus peaks, ensuring no overlap with excipients.
• Developing chemometric models, specifically Principal Component Regression (PCR) and Partial Least Squares (PLS) regression, for quantitative analysis.
• Validating model performance using near-infrared chemical imaging for sample uniformity and comparing model-calculated values against known crystalline drug percentages.

Main Results:

• XRPD successfully identified distinct, non-overlapping peaks for crystalline tacrolimus.
• Chemometric models (PCR and PLS) demonstrated high accuracy (R² > 0.99) in quantifying crystalline tacrolimus across various mixtures.
• The PLS-based model exhibited superior performance with lower error and bias compared to the PCR model.
• Model predictions closely matched the actual crystalline drug percentages in validation formulations.

Conclusions:

• Chemometric-XRPD models are highly effective for the quantitative analysis of crystalline tacrolimus in solid dispersions.
• This approach provides a robust and accurate quality control tool for pharmaceutical formulations.
• The developed model can be applied to predict crystalline drug content, ensuring product consistency and efficacy.