Insights into development of long-acting injectable suspensions

Long acting injectable (LAI) suspensions represent a promising drug delivery platform, offering a number of advantages such as sustained therapeutic effects, improved patient adherence, and reduced dosing frequency for the management of chronic diseases. Moreover, these drug products are of pharmaceutical significance as they provide opportunities to extend the patent life cycle of a drug molecule, as well as opportunities for market differentiation. Despite this, the pharmaceutical development of LAI suspensions remains highly challenging due to their complex drug release mechanisms, undefined critical quality attributes (CQAs), lack of robust in vitro release testing methods and predictive in vitro-in vivo correlation (IVIVC) models. This review provides an in-depth analysis of the current state of LAI suspension development, covering market trends, therapeutic applications, regulatory frameworks, manufacturing aspects, and key formulation CQAs. It highlights recent advancements in physicochemical characterization, in vitro drug release testing methodologies, and the development of IVIVCs and physiologically based pharmacokinetic (PBPK) models. Particular emphasis is placed on the role of particle size, agglomeration behavior, and depot formation in modulating drug release, as well as novel in vitro release testing methods. Additionally, this review outlines the regulatory and technical barriers impeding the development of both innovator and generic LAI suspensions and proposes strategies for future research, including the need for biorelevant release methods and mechanistic modeling approaches. These insights may guide formulation scientists and regulatory bodies in advancing the development and approval of LAI suspensions.