Abstract

Conventional oral controlled-release formulations depend heavily on functional excipients to modulate drug release through mechanisms like swelling, erosion, and diffusion barriers. However, these approaches often increase tablet size, complicate manufacturing, and reduce patient compliance. This study presents a novel formulation strategy that leverages the intrinsic solid-state properties of the active pharmaceutical ingredient (API), specifically crystal polymorphism, to control drug release without the need for added excipients. Using clarithromycin (CAM) as a model, the research highlights a unique phenomenon wherein the metastable anhydrous form (Form I), despite its high solubility and rapid dissolution rate, suppresses drug release when incorporated into tablets. This unexpected behavior is attributed to a spontaneous hydration-induced transition from Form I to Form IV, a hydrated polymorph with lower solubility, upon contact with aqueous media. The transformation generates a dense layer of fine, needle-shaped crystals on the tablet surface, impeding water ingress and delaying disintegration, effectively creating a self-coating, controlled-release system. This excipient-free approach has significant implications for high-dose drugs, improving patient compliance, and simplifying manufacturing. The findings suggest that harnessing polymorphic transitions can revolutionize sustained-release formulation strategies, reducing reliance on excipients and advancing patient-centered drug deliverysystems.

Keywords

crystal polymorphism, drug release modulation, solid-state transitions, clarithromycin polymorphs, oral dosage forms, pharmaceutical formulation design