Physicochemical Properties and Molecular Insights of Favipiravir and Roflumilast Solid Dispersions for COVID-19 Treatment.

Fixed-dose combinations (FDCs) offer significant advantages for patients and healthcare systems by improving adherence and reducing pill burden. However, developing multi-drug formulations remains challenging due to complexities in drug compatibility, stability, and dissolution behavior. The COVID-19 pandemic has necessitated innovative therapeutic approaches. This study aims to develop and evaluate an FDC containing FR (an antiviral drug) and RT (a PDE4 inhibitor) for potential COVID-19 treatment. The proposed dual-layer FDC was formulated to achieve immediate release of RT using Klucel EXF and controlled release of FR using a combination of Klucel HXF and Compritol ATO888. Critical quality attributes, including drug-excipient compatibility, solid-state properties, tablet uniformity, and dissolution kinetics, were assessed. RT and FR quantification methods were developed and validated per international guidelines. Compatibility studies were conducted by combining excipients in fixed ratios with APIs, followed by stability testing. No degradation or adverse interactions were observed between APIs and excipients. RT exhibited rapid dissolution within 30 min, while FR release was effectively controlled through a gel-forming matrix and lipid barrier. Bulk powder and tablet physical parameters met pharmacopeial standards, and content uniformity between layers was maintained. The formulation demonstrated a stable dissolution profile for both drugs, ensuring consistent drug release. The novel FDC of RT and FR exhibits favorable physicochemical properties, a stable dissolution profile, and potential for improved treatment efficacy in COVID-19 patients. By optimizing drug release mechanisms and ensuring formulation stability, this FDC could serve as a pharmaco-economically viable alternative to existing therapies, enhancing patient compliance and treatment outcomes.