Injectable Lipid-Based Depot Formulations: Where Do We Stand?

Abstract

The remarkable number of new molecular entities approved per year as parenteral drugs, such as biologics and complex active pharmaceutical ingredients, calls for innovative and tunable drug delivery systems. Besides making these classes of drugs available in the body, injectable depot formulations offer the unique advantage in the parenteral world of reducing the number of required injections, thus increasing effectiveness as well as patient compliance. To date, a plethora of excipients has been proposed to formulate depot systems, and among those, lipids stand out due to their unique biocompatibility properties and safety profile. Looking at the several long-acting drug delivery systems based on lipids designed so far, a legitimate question may arise: How far away are we from an ideal depot formulation? Here, we review sustained release lipid-based platforms developed in the last 5 years, namely oil-based solutions, liposomal systems, in situ forming systems, solid particles, and implants, and we critically discuss the requirements for an ideal depot formulation with respect to the used excipients, biocompatibility, and the challenges presented by the manufacturing process. Finally, we delve into lights and shadows originating from the current setups of in vitro release assays developed with the aim of assessing the translational potential of depot injectables.

Self-injectable extended release formulation of Remdesivir (SelfExRem): A potential formulation alternative for COVID-19 treatment

“…Reports suggests that while formulations requiring forces above 50 N are injectable, they are administered with greater difficulty ( Cilurzo et al, 2011 ). Injection forces less than 25 N allow easy injection for most depot formulations ( Rahnfeld and Luciani, 2020 ). Injectability profiles have been previously reported to be only a representation of Fmax with some correlation to the dynamic glide force ( Cilurzo et al, 2011 ).…”

“…It is listed in the FDA inactive ingredient database (IID) list for the SC and periodontal routes ( Ahmed et al, 2014 ). An in-situ depot injection involves a less complex manufacturing process compared to solid implants and microparticles ( Rahnfeld and Luciani, 2020 ) and can be developed relatively quickly.…”

<p>Biomedical Applications of Multifunctional Polymeric Nanocarriers: A Review of Current Literature</p>

“…nanoparticles modified with polymeric materials as well as protein/peptide self-assembled nanocarriers. [20][21][22][23][24][25][26][27][28][29] Sketches of selected polymeric nanocarriers are presented in Figure 3.…”

The Phospholipid Research Center: Current Research in Phospholipids and Their Use in Drug Delivery

“…The project by Jai Prakash (University Twente, Enschede, the Netherlands) about immunostimulating liposomes targeting the M2 macrophage to eradicate cancer follows on seamlessly from the work he has completed (see Table 3 and explanations below the table). The project by Lisa Rahnfeld (University Bern, Bern, Switzerland) is about the development of an injectable phospholipid-based depot technology for sustained drug release [ 208 , 209 ]. This project is a follow-up study to the finished project by Paola Luciani (ibid.).…”