Development of Long-Acting Injectable Microspheres
Introduction
Long-acting injectable formulations have been successfully developed for multiple APIs, including small molecules and peptides, resulting in improved patient compliance and enhanced therapeutic outcomes. A common approach involves microencapsulation of the therapeutic agent within biodegradable materials, such as poly(lactic-co-glycolic acid) (PLGA), which can be lyophilized into a dry powder for improved shelf stability. Following a single injection, sustained drug levels in the blood or target tissue for 1 – 3 months can be achieved. Long-acting injectable formulations have been developed to treat a variety of diseases including cancer, psychotic disorders, narcotic dependence, hormone regulation, and periodontal disease [1]. Examples of FDA approved products include Lupron Depot® (leuprolide acetate), Vivitrol® (naltrexone), and Bydureon® (exenatide).
Phosphorex has extensive expertise in the development of long-acting injectable formulations for multiple API types including small molecules, peptides and proteins. Phosphorex can provide a custom scope of work that best suites the properties of the API, stage of development, route of administration, and intended therapeutic outcomes.
Areas of Expertise:
- Pre-formulation
- API Solubility / Stability
- Analytical Method Development
- API loading / In Vitro Release Assays (Figure 1)
- Formulation Development
- Optimization of Particle Size / Size Distribution / API Loading (Table 1)
- Process Development and Scale-up
- Equipment Selection and Process Optimization
- Lyophilization Cycle Development
- Selection of Lyoprotectant
- Tech-transfer to GMP Production
Figure 1. Cumulative in vitro release profile of prototype generic microsphere drug product (solid blue line) versus Reference Listed Drug (RLD) product (dashed green line).
Table 1. Optimization of formulation and process conditions to achieve target particle size (< 20 µm) and drug loading (> 10%w/w).
|
Process |
Particle Size, µm |
Drug Loading, %w/w |
| 1 | 13 | 7.9% |
| 2 | 43 | 10% |
| 3 | 17 | 11% |
References
[1] Jain, A., Kunduru, K. R., Basu, A., Mizrahi, B., Domb, A. J., & Khan, W. (2016). Injectable formulations of poly (lactic acid) and its copolymers in clinical use. Advanced drug delivery reviews, 107, 213-227.