Formulation Properties of Long-Acting Injectable Antipsychotics and the Impact on Administration: Focus on Aripiprazole Lauroxil

Background: Long-acting injectable (LAI) antipsychotics have significant differences in formulation composition, which is an important factor for administration technique. Here, we review formulations of LAIs indicated for schizophrenia treatment and how they impact instructions for use, with a focus on aripiprazole lauroxil.

Methods: The early depot LAIs are formulated as oil-based solutions that do not require mixing prior to injection. However, oil-based solutions tend to be viscous and may cause injection-site reactions (ISRs). New LAI formulations tend to be aqueous-based suspensions that can be less viscous and easier to inject but require resuspension or reconstitution before injection. The formulation properties of currently available LAIs lead to differences in administration.

Results: Among the newer LAIs, aripiprazole monohydrate and olanzapine pamoate lyophilized powders, as well as risperidone powder formed of microspheres, all require reconstitution before administration. Paliperidone palmitate is a ready-to-use aqueous suspension of crystalline particles. Instructions for injection of aripiprazole monohydrate, paliperidone palmitate, and olanzapine pamoate recommend slow speed. Aripiprazole lauroxil is an aqueous-based, ready-to-use suspension of crystalline particles. The aripiprazole lauroxil formulation differs from other LAIs in that the particles are flocculated to facilitate resuspension. Flocculated suspensions are shear-thinning and must be injected rapidly – the viscosity of the injection decreases with higher injection forces. Vigorous shaking and rapid injection are key aspects of administration of aripiprazole lauroxil.

Conclusion: Advances in formulation technology have been essential for increasing LAI options for patients with schizophrenia. Successful administration requires awareness of the differences in formulation design and the impact on injection technique.