Early detection and assessment of invisible cracks in compressed oral solid dosage forms

Abstract

In the pharmaceutical manufacturing industry, real-time in situ quality monitoring for detecting defects at an early stage is a desirable ability, especially in high-rate production, to minimize downstream quality-related issues, financial losses, and timeline risks. In this study, we focus on the early detection of crack formation in compressed oral solid dosage (OSD) forms at its onset before complete delamination and/or capping in downstream processing. The detection of internal tablet cracks related to local micro-stress/strain states, internal granularity (texture), and micro-structure failures is rather unlikely by traditional testing methods, such as the USP reference standards for friability, fracturing, or hardness testing. In addition, these tests do not permit the objective and quantitative evaluation of the influence of formulation and process parameters, which are critical for the development of high-quality drug products manufactured at high rates on a large scale. Internal cracks (potentially resulting in ‘capping’ and/or ‘lamination’) under high-strain compaction of highly visco-elastic powder materials are a common failure mode. In the current study, two approaches are introduced and utilized for non-destructively detecting and evaluating hidden cracks in pharmaceutical compacts based on (i) varying axial load–displacement measurements and (ii) ultrasonic reflection ray tracing. The reflection ray tracing technique is a non-destructive, inexpensive, rapid, and material-sparing approach, which makes it advantageous for real-time quality monitoring and defect characterization applications. The varying axial load–displacement technique is more suitable for analytical studies, especially in the design and development phases of compressed OSD products. In this study, as a model application, utilizing these two approaches, it is demonstrated how internal and external cracks can be detected, localized, characterized, and analyzed as a function of disintegrant ratio and main compression force. Various uses of these two techniques in practice, such as in Continuous Manufacturing (CM) and Real-Time Release Testing (RTRT), are also discussed.