Ionic Liquids as Enabling Formulations for Poorly Bioavailable Drugs

Oral delivery of active pharmaceutical ingredients (APIs) is the most predominant route of drug administration. The bioavailability of orally administered drugs is mainly dependent on their aqueous solubility and membrane permeability properties. Ionic liquid forms of drugs, known as API-ILs, have emerged as a promising solution to address challenges posed by poorly bioavailable drugs and solid-state stability. These organic salts, typically liquid at room temperature, have demonstrated the ability to enhance both aqueous solubility and membrane permeability of APIs. To further optimize their properties, lipidic excipients were successfully incorporated into API-ILs in this study. However, for the routine integration of liquid API-ILs into oral solid dosage forms, challenges related to ease of handling and manufacturing need to be addressed. Therefore, a comprehensive framework has been developed for transforming API-ILs and their lipidic multi-component solutions into solid presentations using spray encapsulation with various polymers. Multiple APIs spanning all BCS Classes were successfully transformed into ionic liquids and solidified, with subsequent evaluation of the solid API-IL products for dissolution, membrane permeability, stability, and powder flow properties, gauging their suitability for incorporation into oral solid dosage forms. Finally, two distinct isolation-free manufacturing processes were devised for the synthesis, purification, and solidification of API-ILs, with the first method focusing on hydrophilic API-ILs using ion exchange resins and the second method targeting lipophilic, self-emulsifying API-ILs through liquid-liquid extraction via a concentric annular separator.