The development of oil-based long-acting injectable formulations (LAIF) involves creating a formulation where an active drug is dissolved or suspended in an oil-based medium, allowing for a sustained release of the drug over an extended period. These formulations are generally administered intramuscularly or subcutaneously and are designed to provide long-lasting therapeutic effects, reducing the frequency of administration compared to immediate-release formulations.
They are particularly desirable in chronic conditions requiring steady medication levels, enhancing patient compliance, and improving treatment outcomes. Oil-based depot injections can also provide localised delivery of drugs, minimising systemic side effects. Although typically used for controlled release, in some cases, the choice of an oil-based formulation may also be driven by the poor solubility of the drug in aqueous solutions, even when a faster release is the target.
Understanding the principles of diffusion is essential for optimising the performance of oil-based injectable formulations. The diffusion process governs how the drug moves from the oil phase into the surrounding aqueous environment of the body, influencing the release rate and overall efficacy of the formulation. By applying mathematical models of diffusion and the oil-water partition coefficient (Kow), formulators can make informed decisions regarding excipient selection and formulation design, ensuring that the drug is released in a controlled and predictable manner to achieve the desired therapeutic effect.
Background
When an oil-based solution is injected into the body, typically intramuscularly, it forms a depot or reservoir at the injection site. This depot releases the drug at a slower rate due to the oil-based nature of the solution. The release process involves diffusion, which is the movement of molecules from an area of higher concentration (the depot) to an area of lower concentration (the surrounding tissues). This process is driven by the concentration gradient and influenced by the oil-water partition coefficient (Kow) of the drug.
The diffusion coefficient (-D) plays a crucial role in determining the rate at which drug molecules move through the medium. Factors affecting the diffusion coefficient include the size and shape of the drug molecules, the viscosity of the oil, and the temperature. There are two primary mechanisms for drug release from an oil-based depot: passive diffusion and partitioning/redistribution. Passive diffusion, driven by the concentration gradient, is the main mechanism, while partitioning between the oil phase and the aqueous environment of the body tissues also occurs. Once the drug diffuses into the aqueous phase, it can be taken up by surrounding tissues or enter the bloodstream. The diffusion process can be described mathematically according to Fick’s first law of diffusion which describes steady-state diffusion, where the flux (amount of free/ dissolved drug per unit area per unit time) is proportional to the concentration gradient.
