Characterization of drug-cyclodextrin formulations using Raman mapping and multivariate curve resolution

Area of Science:

• Pharmaceutical Sciences
• Analytical Chemistry
• Materials Science

Background:

• Understanding drug-excipient interactions is crucial for pharmaceutical formulation development.
• Cyclodextrins are commonly used excipients that can influence drug stability and bioavailability.
• Characterizing the physical and chemical state of the active pharmaceutical ingredient (API) within formulations is essential.

Purpose of the Study:

• To characterize drug-excipient interactions between an API and various cyclodextrins using Raman chemical imaging.
• To investigate sample heterogeneity and quantify recrystallized API within these mixtures.
• To validate Raman mapping as a sensitive analytical technique for pharmaceutical analysis.

Main Methods:

• Raman chemical imaging and mapping were employed for detailed analysis.
• Multivariate curve resolution-alternating least squares (MCR-ALS) was used for data analysis and quantification.
• Scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDX) and X-ray powder diffraction (XRPD) were used for validation.

Main Results:

• Raman mapping provided detailed insights into drug-excipient interactions and sample heterogeneity.
• MCR-ALS successfully quantified the amount of recrystallized pure API.
• Raman mapping demonstrated superior sensitivity in detecting pure crystalline API compared to XRPD.

Conclusions:

• Raman chemical imaging is a powerful tool for characterizing complex drug-excipient interactions.
• The study validates Raman mapping for detecting trace amounts of crystalline API, surpassing the limits of conventional methods like XRPD.
• This technique offers significant potential for quality control and formulation development in the pharmaceutical industry.