Unlocking the Therapeutic Potential of Iloperidone in the Treatment of Schizophrenia: An Insight into Biopharmaceutical Challenges, Formulation Strategies, and Future Prospects

Iloperidone (ILP) is a United States Food and Drug Administration (US FDA) approved atypical antipsychotic drug. It is a frequently prescribed drug for the treatment of Schizophrenia. However, the oral delivery of ILP is challenging because of its lipophilic nature, high first-pass metabolism, and poor bioavailability. In the last decade, many novel delivery approaches have been developed to address the challenges, including lipid-based nanoparticulate systems, inclusion complexes, co-crystals, nanosuspension, and depot injections. Furthermore, co-delivery strategies with antioxidants (e.g., Idebenone) have been explored to mitigate oxidative stress and associated extrapyramidal side effects linked to chronic ILP therapy. Therefore, this review provides an insight into novel delivery approaches explored for augmenting the bioavailability and therapeutic efficacy of ILP in schizophrenia. Furthermore, a crisp discussion on the ILP development, pharmacology, dosing strategies, physicochemical, and pharmacokinetic parameters has also been added. This understanding will assist formulation scientists in developing safer and effective ILP formulations in the coming years. Lastly, a perspective on intranasal delivery of ILP has been presented to circumvent the blood-brain barrier and improve its brain accumulation.