Quantitative solid-state analysis of three solid forms of ranitidine hydrochloride in ternary mixtures using Raman...

Area of Science:

• Analytical Chemistry
• Pharmaceutical Analysis
• Spectroscopy

Background:

• Ranitidine hydrochloride exists in multiple solid forms, impacting its pharmaceutical properties.
• Accurate quantification of these forms in mixtures is crucial for drug development and quality control.

Purpose of the Study:

• To develop a reliable quantification procedure for ternary mixtures of ranitidine hydrochloride solid forms.
• To evaluate the influence of sample mixing methods on quantification model accuracy.
• To compare the performance of X-ray powder diffraction (XRPD) and Raman spectroscopy for this analysis.

Main Methods:

• Preparation of ternary mixtures using manual mixing (MM) and ball mill mixing (BM).
• Analysis of samples using XRPD and Raman spectroscopy.
• Application of Principal Component Analysis (PCA) for mixing method assessment and Partial Least Squares (PLS) regression for quantification.

Main Results:

• Ball mill mixing with 12 mm balls (BM12) generally yielded better sample homogeneity.
• PLS regression models achieved root mean square error of prediction (RMSEP) of 5.0-6.9% for XRPD and 2.5-4.5% for Raman spectroscopy.
• Raman spectroscopy demonstrated superior performance over XRPD for accurate quantification.

Conclusions:

• XRPD and Raman spectroscopy, coupled with PLS regression, are effective for quantifying ranitidine hydrochloride solid forms in mixtures.
• Raman spectroscopy offers a more precise method for analyzing these ternary mixtures.