Long-acting injectables (LAIs) are therapeutics designed with a sustained drug delivery system, meaning that medication is gradually released into the body over an extended period. Prolonging the release of active pharmaceutical ingredients (APIs) is a concept that has been around for some time; oral formulations have been on the market since 2001, while the first long-acting injectables were approved by the US Food and Drug Administration (FDA) in the early ‘90s. However, long-acting injectables are increasingly preferable for numerous reasons, which we will explore later in this article.
Despite enormous uptake and widespread applicability—long-acting injectables have proven successful in hormone replacement therapy, pain treatment, and more—processing LAR injectables remains challenging. Many candidate materials are available as drug delivery vehicles, but biodegradable microspheres occupy the cutting-edge. They can be readily combined with various APIs and formulated into depot injections with demonstrable success at prolonging drug delivery with outstanding efficacy. So, how does it work?
What are Long-Acting Injectables?
Long-acting injectables are sometimes called “depot” injections as they “deposit” a drug load into tissue, creating a store of medication at the injection site that is gradually absorbed over the following weeks—or even months. The compound material makes this sustained release possible.
Polymeric microspheres, for example, encapsulate API molecules and gradually degrade in vivo, slowly releasing the drug load into the body. The rate at which these microspheres release active compounds depends on their composition, shape, and size, meaning drug manufacturers can finely tailor a drug’s release kinetics to optimise therapeutics for better pharmaceutical outcomes. A simple example is that a smaller microsphere will likely release its load quicker than larger particles. Thus, drug release rates can be altered by fine-tuning microsphere particle size and particle size distribution (PSD). As far as composition is concerned, there is a growing range of biocompatible candidate polymers that may be suitable for depot injections. Polylactic acid (PLA) and polyethylene glycol (PEG) are among the primary candidates as they degrade enzymatically over time when injected via a standard syringe.
What are the Advantages of Long-Acting Injectables?
LAIs require less frequent dosing, making it easier for patients to stay on their medication regimen.
LAIs can be administered less frequently, which can be more convenient for patients who have difficulty remembering to take their medication or who may have mobility issues.
As they can be injected into specific parts of the body, LAIs allow clinicians to target localised anatomical areas. This not only improves the drug’s specificity but also reduces the risk of systemic exposure.
LAIs can be more cost-effective over time as they require fewer clinic visits and less frequent medication refills.
Reduced risk of overdose
Because LAIs provide a steady and sustained level of the active drug, there is less risk of overdose, particularly when compared to oral medications.
Reduced risk of medication interactions
LAIs reduce the chance of medication interactions as they do not have to be taken with food or in coordination with other medications
Reduced risk of diversion
LAIs are less likely to be shared or sold than oral medications, which reduces the risk of diversion and abuse.
Stable blood levels
LAIs provide a steady and sustained level of the active drug in the body, which can help improve the treatment’s efficacy and reduce the likelihood of breakthrough symptoms or side effects.
How are Long-Acting Injectables Processed?
Long-acting injectable medications are typically made using one of two methods: microencapsulation or depot formulation. Microencapsulation is the technique already discussed, where a polymeric material surrounds the API to create microspheres, which are then suspended in an aqueous phase. Depot formulation, meanwhile, is a deviation from this route. The API is still combined with a polymer, but it is uniquely formulated to deposit as a solid store following injection. Both methods provide the required sustained release, but encapsulation often yields more consistent results.
Interested in Learning More about Polymers in LAR Medication?
Powder Systems Ltd (PSL) is delighted to once again be hosting the Microsphere Summit – a two-day event bringing together developers of new drugs with specialist manufacturers in an interactive setting. The Summit provides an impressive programme of conferences, workshops and training sessions and is the ideal forum for discussions surrounding polymeric microspheres in LAR medication. We will be discussing all aspects of long-acting release injectable processing, including polymer selection and microsphere formulation methods. Visit our website today or download our Summit Programme now for more details.