Inulin‐Lipid Core–Shell Microcapsules Target the Gut Microbiota and Mimic the Pharmaceutical Food Effect for Improved Oral Antipsychotic Delivery

Abstract

The oral delivery of most atypical antipsychotics is severely challenged by their low oral bioavailability and significant food effects that necessitate patient compliance. Lipid formulations are an attractive delivery system for overcoming the dosing challenges of antipsychotics, but their negative impact on the gut microbiota can interfere with the pharmacodynamic response through disruption of the gut‐brain axis. Here, novel gut microbiota‐targeting microcapsules are engineered to provide a multifunctional approach for improving both the pharmacokinetic and pharmacodynamic properties of the antipsychotic, lurasidone. The microcapsules are comprised of a lipid core that facilitates the solubilization and oral absorption of the lipophilic drug and an outer carbohydrate polymer (inulin) shell that positively modulates the gut microbiota by facilitating microbial fermentation. Fed‐fasted variability in lurasidone solubilization is mitigated through microencapsulation with inulin‐lipid microcapsules (ILM), while microbiota enrichment is coupled with enhanced serotonin levels in the small intestine, faeces, and plasma. The realization of multifunctional ILM confirms the pharmacokinetics and efficacy of mental health therapies, such as antipsychotics, can be optimized through strategic encapsulation within functional formulations that target the gut microbiota for effective modulation of the gut‐brain axis.

The Oral Bioavailability of Lurasidone is Impacted by Changes to the Gut Microbiome: Implications for Antipsychotic Therapy

“…Furthermore, it is hoped that the exploration of lurasidone's pHdependent solubility spur strategies to maximise solubility, absorption and bioavailability, for example as achieved by Meola et al through the formulation of a lipid-based nanostructure and porous silica nanostructure which enhanced bioavailability of lurasidone by 8.8-fold. 52 .…”