Microsphere Feasibility Program for Long-Acting Injectables
Long-acting injectables (LAIs), including those containing bioabsorbable microparticles, are an area of growing interest in the pharmaceutical industry. LAIs are high-value products that offer an appealing route to improved patient compliance and reduced administration frequency. These polymer-based systems may be able to encapsulate large quantities of API for parenteral or ophthalmic administration and enable the delivery of both small and large molecules for weeks or months at a time.
Why partner with LLS Health?
LLS Health is a leading solutions provider for long-acting injectables, and we are uniquely equipped to address the complex design, development, and manufacturing challenges that accompany microparticle-based formulations and microparticle preparation methods. We have experience in GMP manufacturing to support complex drug products. We have manufactured several GMP batches of microspheres to support phase I and II clinical trials for both large pharma and virtual companies.
Long-acting injectable formulations are complex products that can take several forms, including microspheres and gel depots. LLS Health utilizes a range of manufacturing techniques and leverages strong relationships with polymer suppliers to design formulations that meet your target product profile. Whether your long-acting injectable is based on microsphere technology or another approach, we are a flexible, full-service partner equipped to take your project from early-stage development GMP production.
Our seasoned staff has experience handling highly potent APIs (hormones, steroids, cytotoxics), controlled substances (Schedule I-V), and large molecules (proteins, peptides, nucleotides). We have a full suite of analytical capabilities for characterizing microspheres in-house. Our team is well-versed in analytical method development and validation, including in vitro release testing. We also offer a range of customizable ICH stability programs.
Frequently Asked Questions
How are long-acting depot injections supplied?
Long-acting injectables based on microsphere technology are supplied as lyophilized powders for reconstitution. The freeze-dried powder is accompanied by a diluent for injection.
Why develop a long-acting injectable with microspheres?
Long-acting drug delivery systems offer the potential for targeted drug release, lower dosage requirements, and improved patient compliance by replacing daily pills or injections. Well-designed microspheres can be tailored to a specific API and application, leading to improved bioavailability, stability, and pharmacokinetics as well as intellectual property and life-cycle management opportunities.
Which long-acting injectables consist of microspheres today?
14 FDA-approved products consist of microspheres, including multiple blockbuster products—Lupron Depot®, Sandostatin® LAR, Risperdal Consta®, and others. The first microsphere product was approved by the FDA in 1989, but the technology remains relevant today, and several microsphere products have been approved since 2017. Microsphere products offer strong IP protection and long product lifecycles due to their complexity, making them an appealing option for new product development.
What kinds of APIs are amenable to microsphere technology? Can you load large molecules into microspheres?
Both small and large molecules—including proteins, peptides, and nucleic acids—have been encapsulated in polymeric microspheres. Highly potent compounds such as cytotoxic APIs are well-suited for microsphere technology.
Can you modify the polymer in microspheres?
Yes—polymer selection for microspheres is highly customizable. There are a number of commercially-available PLGA chemistries with varying molecular weights and LA:GA ratios that offer control over microsphere properties and drug release. If an off-the-shelf polymer does not meet your target product profile, we can leverage our strong relationship with Corbion to develop a custom solution.
How do you make microspheres?
Microspheres are typically produced via an emulsion-based process follow by solvent evaporation. Based on the properties of the API, such as hydrophobicity, a single- or double-emulsion process may be employed. Once the particles are created, a filtration step is used to segregate microspheres by size and achieve a tighter particle size distribution. These particles are then combined with other excipients, as appropriate, and lyophilized to obtain a powder for reconstitution and parenteral administration. We are currently evaluating new technologies to more efficiently manufacture and filter microspheres for our clients. This is part of our commitment to a broad technology portfolio that increase your odds of success.