High-core loading long acting Injectables (LAI) for Biologics

For high-dose biologics, commercially practical injection volumes may require unusually high drug loading. In some development programs, drug content may need to approach or exceed 50% by mass. The necessary loading depends on potency, target exposure, particle density, syringeability, injection volume and intended release duration.

Initial burst release occurs when drug located at or near the particle surface dissolves rapidly after injection. Water may also penetrate pores and interconnected drug-rich regions within the polymer matrix. This can release a substantial portion of the payload before the intended sustained-release phase begins.

Several complementary formulation strategies can be used to reduce early release while maintaining a high biologic payload. The appropriate route depends on the physicochemical properties of the API, the polymer system and the required release duration.

Hydrophobic ion pairing temporarily complexes an ionizable biologic with an oppositely charged counter-ion. Lower aqueous solubility may reduce premature diffusion from the polymer matrix. Performance depends on counter-ion selection, complex stability, processing conditions and recovery of active biologic after release.

A core-shell structure physically separates a drug-rich core from the external environment using a drug-free or drug-poor polymer shell. When the shell is continuous and sufficiently dense, it can reduce surface-associated API and provide an additional barrier to water ingress and drug diffusion. Shell thickness, defects, porosity and degradation behaviour determine the resulting release profile.[5]

Rapid precipitation or solidification can immobilize the biologic before it migrates to the droplet surface or separates into large drug-rich domains. Solvent exchange, drying conditions and solid-state transitions must be controlled to protect molecular integrity and activity.

IN-AIR MICROFLUIDICS™ is a channel-free particle-manufacturing platform in which microscale liquid jets interact and form droplets in air. Published work demonstrated monodisperse emulsions, particles and fibres with diameters of approximately 20–300 µm at rates 10–1000 times higher than the chip-based droplet microfluidic configurations used for comparison.[1]

For sustained-release biologics, the platform is relevant because droplet formation, material distribution and solidification can be controlled without enclosed microchannels. This creates routes to structured particles while reducing the channel-clogging constraints associated with conventional microfluidic chips.

By running concentric fluid streams through an in-air coaxial nozzle, IAMF can cleanly encapsulate a dense, >50% biologic inner core directly inside a pure, drug-free outer polymer shell. The pure polymer shell serves as an uncompromised physical gatekeeper, entirely eliminating the presence of surface-bound drug molecules that typically cause the initial burst release.[7,8,9]

Droplets may undergo solvent evaporation, nonsolvent-induced phase separation or another solidification process during or immediately after formation. The competition between external mass transfer and internal molecular diffusion influences whether material accumulates near the surface or remains more uniformly distributed. Under suitable conditions, rapid surface solidification can create a denser outer region surrounding a porous or payload-rich interior.

In-air microfluidics offers relatively mild, low-shear processing conditions and short residence times, which may help preserve sensitive and high-value materials during particle formation. Its scale-up strategy is based on numbering up individual nozzles in parallel while maintaining comparable operating conditions at each nozzle. This approach may reduce material consumption during feasibility studies and support more predictable process translation toward larger production volumes.