Raman spectroscopy as process analytical technology tool for monitoring atomic layer deposition (ALD) of drug particles

Process monitoring of product quality attributes using spectroscopic tools is a prerequisite to implement process analytical technology (PAT) to achieve consistency in process performance and product quality. Raman spectroscopy is an established tool for real-time monitoring of product quality attributes during pharmaceutical manufacturing. This paper proposes real-time monitoring of atomic layer deposition (ALD) coating on an active pharmaceutical ingredient (API) using Raman spectroscopy. Palbociclib, a cytotoxic drug for treating advanced breast cancer, is used to develop the model. Product quality attributes such as homogeneity, surface modifications, and dissolution profile were measured using Raman spectroscopy, X-ray diffraction, and dissolution testing, respectively. The principal least squares (PLS) model developed had a cumulative coefficient of determination of 0.988. The proposed approach has been demonstrated to accurately measure the number of ALD coating cycles and identify the type of metal oxide coating. Hence, it can offer an effective method for online monitoring of coating during ALD.

Automated summary

This paper proposes a method for real-time monitoring of atomic layer deposition (ALD) coating on an active pharmaceutical ingredient (API) using Raman spectroscopy, with Palbociclib as the model drug. By measuring product quality attributes such as homogeneity, surface modifications, and dissolution profile, and developing a principal least squares (PLS) model, the proposed approach accurately monitors the ALD coating online.