LOW DOSE TABLET MANUFACTURING: INFLUENCE OF EXCIPIENT SURFACE ROUGHNESS AND IN-LINE PROCESS MONITORING USING NIR SPECTROSCOPY

Abstract

Achieving content uniformity for low dose tablet formulations can present several processing and formulation challenges. The uniformity of the starting powder blend constitutes the first step in ensuring content uniformity of the tablets. Traditionally, quality assessments of tablets and their intermediates are based on tests conducted on limited samples. However, the samples obtained are rarely representative of the production batch. Furthermore, the analyses of excipients have been neglected. This project comprised two main parts concerned with the low dose tablet manufacturing. The first investigated the role of excipient (lactose) surface roughness in ordered mixing and physical stability of the ordered mixture. Surface roughness of lactose particles showed significant influence on bulk powder flow and capacity to retain drug particles on their surfaces. The second dealt with in-line monitoring of blending and tabletting unit operations using near infrared (NIR) spectroscopy. Findings of this study showed that with the unique features of NIR spectroscopy, i.e. high speed sampling and rapid spectral acquisition, simultaneous distribution of both drug and excipients could be monitored with high accuracy in an efficient and non-destructive manner. This would not have been possible with traditional content uniformity analysis. Findings of this project represent a step forward in achieving the objectives of continuous quality improvement of pharmaceutical dosage forms as laid out by US-FDA process analytical technology (PAT) guidelines.