Exploring formulation options for extended release minitablets

Compared to conventional tablets, minitablets have several advantages, like acceptance for patients with swallowing difficulties (from pediatric to geriatric) and high flexibility in dosing. Despite these advantages, minitablets are challenging for extended release (ER) dosage forms. We explored different ER minitablet formulations for Compound A with the aim of maintaining drug plasma concentrations over 24 h. Compound A is a BCS class II drug with pH-dependent solubility and was available as monosodium monohydrate salt and its parent free acid form. To reduce pill burden, high drug load in the final drug product was in scope. Minitablets were manufactured by either wet or melt granulation. The formulation screening was based on compendial dissolution testing to enable sufficient throughput. Subsequently, the impact of certain physiological luminal pH on drug release was explored in a biorelevant test method (multi-stage dissolution test). We demonstrated that by combining the right API form, hydrophobic matrix formers as well as hydrophilic release components, minitablets that enable the extended release of Compound A over 24 h were feasible. A defined material-sparing pathway to adjust release profiles combined with targeted biorelevant drug release testing provides a novel approach to develop ER minitablets in a relatively short time.