The objective of this study was to develop phospholipid-based injectable phase transition in situ gels (PTIGs) for the sustained release of Brexpiprazole (Brex). Phospholipid (Lipoid S100, S100) and stearic acid (SA) were used as the gel matrix which was dissolved in biocompatible solvent medium-chain triglyceride (MCT), N-methyl pyrrolidone (NMP), and ethanol to obtain PTIGs solution. The Brex PTIG showed a solution condition of low viscosity in vitro and was gelatinized in situ in vivo after subcutaneous injection. Both in vitro release assay and in vivo pharmacokinetics study in SD rats displayed that Brex in PTIGs could achieve a sustained release, compared with brexpiprazole solution (Brex-Sol) or brexpiprazole suspension (Brex-Sus). The Brex-PTIGs had good degradability and biocompatibility in vivo with rare inflammation at the injection site. Among the three Brex-PTIG formulations, Brex-PTIG-3 with the SA in the formulation had the greatest gelation viscosity, the lowest initial release rate, and the most stable release profile with sustained release of up to 60 days. The above results indicated that, as a novel drug delivery system, the Brex-PTIGs offered a new option for the clinical treatment of patients with schizophrenia.
Keywords: In situ gel; Long-acting injection; Phospholipids; Schizophrenia; Sustained-release.
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