Enhanced bioavailability and efficacy in antimalarial treatment through QbD approach enteric encased inclusion delivery

<b>Aim:</b> In this study, we aimed to prepare enteric encapsulated spheroids containing inclusion complex using quality by design approach.<b>Methods:</b> A Box-Behnken design was employed to determine effects of variables on selected responses. Risk assessment was conducted using Ishikawa fishbone diagram. A model with a <i>p</i>-value was less than 0.5 for being a significant error of model was determined based on significance 'lack of fit' value. Spheroids were formulated using the extrusion spheronization technique and were characterized using analytical techniques.<b>Results:</b> <i>In vitro</i> release was performed in both acidic (pH 1.2) and simulated intestinal (pH 6.8) conditions. Permeability studies demonstrated tenfold enhancement compared with arteether. <i>In vivo</i> studies further validated increase of 51.8% oral bioavailability. <i>Ex vivo</i> studies revealed 3.4-fold enhancement in antimalarial activity compared with arteether.<b>Conclusion:</b> These findings highlight effectiveness of inclusion complexation technique as a viable approach to enhance solubility and bioavailability for drugs with low aqueous solubility.