High-dose modified-release formulation of a poorly soluble drug via twin-screw melt coating and granulation

Abstract

Favipiravir, a high dose antiviral drug effective for oral treatment for COVID-19, with poor water solubility is formulated using a simple, low-cost melt coating and granulation methodology. High-dose (82.5 % w/w API) tablets (600 mg and 800 mg) with desired release profiles are developed while minimizing excipient burden.

First, twin-screw melt coating and granulation (MCG) of Favipiravir, using Poloxamer P188 as a binder as well as a surfactant, was utilized to create Favipiravir granules with high solubility and tabletability. These granules were then blended with a small amount of extra-granular ingredients (high molecular weight Hydroxypropylmethyl Cellulose and Magnesium Stearate) and compacted into tablets with desired controlled-release tablets.

Results demonstrate that the application of MCG to coat and granulate a poorly soluble drug, using a low melting point surfactant as a binder and wetting agent, can be an effective approach to manufacture high-dose modified release formulations for low solubility drugs that are common in the treatment of infectious diseases, cancer, autoimmune diseases, and many other conditions.

Materials

The following powder materials and chemicals were used in this work: Favipiravir was purchased from Selleck Chemicals LLC (Houston, TX). Two types of poloxamers, Kolliphor® P407 Geismar (P407) and Kolliphor® P188 Geismar (P188) were tested as low cost and low melting point hydrophilic binders (kind gift of BASF Corporation, Florham Park, NJ). Croscarmellose Sodium (CMCNa, Spectrum Chemical Mfg. Corp., NJ) was used as an intra-granular super-disintegrant, Hydroxypropyl Methylcellulose.

Shashwat Gupta, Thamer Omar, Qiushi Zhou, James Scicolone, Gerardo Callegari, Atul Dubey, Fernando Muzzio,
High-dose modified-release formulation of a poorly soluble drug via twin-screw melt coating and granulation, International Journal of Pharmaceutics, 2024, 125090, ISSN 0378-5173, https://doi.org/10.1016/j.ijpharm.2024.125090.