Tablet Compression and Performance of Artocarpus altilis as a Starch-Rich Natural-Source Excipient with Different APIs

Background/Objectives: Excipients play a key role in the manufacturability and performance of solid oral dosage forms, particularly for drug candidates with diverse solubility, permeability, and mechanical properties. Understanding excipient behavior during tablet compression is essential for robust formulation design. Starch-rich natural-source material have emerged as promising candidates due to their availability and favorable deformation behavior. However, there is limited understanding of their tablet compression performance and interactions with active pharmaceutical ingredients (APIs). This study aimed to evaluate the tablet compression behavior and functional performance of a starch-rich natural-source excipient prepared from whole Artocarpus altilis fruit material when formulated with APIs representing all four classes of the Biopharmaceutics Classification System. Methods: Tablets were prepared using a hydraulic press at compression pressures ranging between 296 and 591 MPa. Model APIs included acetaminophen, clarithromycin, vitamin C, and berberine hydrochloride. Tablet compression behavior was characterized using tabletability, compressibility, and compactability profiles, while tablet performance was evaluated through friability, disintegration, and dissolution testing. Results: Densification behavior was controlled primarily by the Artocarpus altilis excipient, whereas tensile strength development and compactability were strongly influenced by API properties. Formulations containing clarithromycin and berberine HCl exhibited enhanced tabletability and compactability, achieving higher tensile strengths at comparable solid fractions. Acetaminophen and vitamin C formulations showed limited strength gains despite similar densification. Formulations containing clarithromycin and berberine HCl maintained low friability, while enabling rapid disintegration and dissolution in acetaminophen and vitamin C formulations. Conclusions: Tabletability and compactability trends varied among formulations, likely reflecting differences in API physical properties and formulation-dependent interparticle interactions, whereas compressibility primarily reflected excipient-controlled densification. Distinct trends were observed across BCS classes, with low-solubility APIs producing stronger tablets and highly soluble APIs showing lower mechanical strength and faster disintegration. Overall, Artocarpus altilis functions as a mechanically robust yet performance-adaptive excipient suitable for tablet formulations across diverse biopharmaceutical contexts.