Image-Based Quantification of Amorphous Solid Dispersion Tablet Formulation Disintegration Profiles in a Custom USP-2 Apparatus

Abstract

Abstract Amorphous solid dispersions (ASDs) are single-phase molecular mixtures of amorphous drug and polymer designed to enhance solubility, inhibit crystallization, and improve release rate, increasing bioavailability. During dissolution, water lowers the glass-transition temperature, triggering gelation and polymer chain mobility. This slows erosion compared to that in neat drug systems. Since the tablet surface area controls drug release onset and rate, its quantitative assessment is vital for predicting dissolution and optimizing ASD performance. Traditional methods like United States Pharmacopeia disintegration testing often rely on visual endpoints and may lack sensitivity to formulation nuances. This tool is often being used in the early stages of formulation development, and it is not an efficient testing method for eroding drug product erosion testing. Imaging techniques, such as magnetic resonance imaging and X-ray microtomography (μCT), are resource-intensive, while mass loss tracking is laborious, inefficient, and prone to reproducibility issues. This project introduces a novel image-based disintegration method using a custom USP-2 apparatus with camera monitoring, directly correlating disintegration/erosion mechanisms with dissolution performance. The study includes apparatus design, formulation development, and image analysis. The erosion and dissolution profile of Ritonavir-PVPVA-based ASD (20% drug loading) formulations with different levels of disintegrants, compressed under two different compression forces, were studied with the USP-2 custom-designed device. Erosion was quantified via time-lapse imaging algorithms that segmented tablet boundaries to calculate the longitudinal and transverse surface area profiles. Findings confirm the method’s viability for erosion profiling as a robust method for quantifying release mechanisms. Compression force across the range (8−10 kN) revealed negligible influence on erosion, as shown by consistent profiles. The formulation that contained high microcrystalline cellulose (MCC) and no lactose showed swelling, followed by erosion in its release mechanism, while a formulation with low MCC and high lactose exhibited a purely erosion-based release mechanism. This method improves formulation predictability and provides insights for ASD drug product release mechanisms.