Pharmacokinetics of Long-Acting Aqueous Nano-/Microsuspensions After Intramuscular Administration in Different Animal Species and Humans—a Review

Formulating aqueous suspensions is an attractive strategy to incorporate poorly water-soluble drugs, where the drug release can be tailored to maintain desired release profiles of several weeks to months after parenteral (i.e., intramuscular or subcutaneous) administration. A sustained drug release can be desirable to combat chronic diseases by overcoming pill fatigue of a daily oral intake, hence, improving patient compliance. Although the marketed aqueous suspensions for intramuscular injection efficiently relieve the daily pill burden in chronic diseases, the exact drug release mechanisms remain to be fully unraveled. The in vivo drug release and subsequent absorption to the systemic circulation are influenced by a plethora of variables, resulting in a complex in vivo behavior of aqueous suspensions after intramuscular administration. A better understanding of the factors influencing the in vivo performance of aqueous suspensions could advance their drug development. An overview of the potential influential variables on the drug release after intramuscular injection of aqueous suspensions is provided with, where possible, available pharmacokinetic parameters in humans or other species derived from literature, patents, and clinical trials. These variables can be categorized into drug substance and formulation properties, administration site properties, and the host response towards drug particles. Based on the findings, the most critical factors are particle size, dose level, stabilizing excipient, drug lipophilicity, gender, body mass index, and host response.