Challenges and innovations in long-acting injectable formulations: can formulation design space be rationalized?

Objectives: To date, ~70 long-acting injectable (LAI) formulations have been developed. More than half of these formulations consist of oily solutions and suspensions containing poorly water-soluble drugs. However, numerous drugs do not fall into the category of poor solubility, such as hydrophilic small molecules, nucleic acids, peptides, and proteins. These drugs are typically formulated using biodegradable poly(lactide-co-glycolide) polymers. An important question to consider is whether there are guiding principles for selecting appropriate drugs for LAI formulations. The historical advancements and challenges associated with LAI formulations were examined to identify indicators that may predict effective drug candidates for this type of delivery system.

Key findings: Several properties of drugs, including water solubility, lipophilicity, tissue permeability, half-life (t1/2), and effective dosage, were analysed in relation to the development of LAIs. This study investigated several parameters to forecast formulation success, with a focus on achieving an optimal balance between the drug's partition coefficient (logP), which reflects both water solubility and cellular permeability, and the effective dose.

Summary: The current overview of recent innovations and formulation considerations indicates that a systematic approach, integrating two key parameters, logP and the effective dose of a drug, may be employed for the preliminary screening of drugs that have the potential to be formulated into LAIs with a higher probability of success in clinical applications.