Development of High Drug Load Multiparticulate Beads Using an Extrusion-Spheronization Process
Purpose
- Drug X is high solubility, high permeability BCS/DCS I small molecule drug.
- High dose and potential pediatric indication required multiparticulate formulation with not less than 80% drug loading to achieve flexible and low quantity dosing with potential for modified release via functional coating.
- Extrusion-spheronization is one of the most common processes to produce multiparticulate formulations, providing numerous advantages such as narrow particle size distribution, smooth coatable surfaces, relatively fast processing times.
- However, for highly soluble drugs, achieving a high drug loading in multiparticulates using extrusion-spheronization can be challenging.
- In this study, the impacts of formulation composition (grade of Avicel and Syloid content), processing parameters for wet massing and extrusion-spheronization on multiparticulate formation were investigated. An optimized composition and manufacturing process were identified.
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Conclusions
- Extrusion- spheronization is one of the most common processes for producing multiparticulate formulations.
- Achieving high drug loading for highly water soluble drugs can be challenging.
- In this study, a multiparticulate formulation with size range between 600 – 1000 μm and drug loading of 80% w/w was achieved for a BCS / DCS I drug.
- High density filler Avicel PH301 MCC was found to be a better excipient for high drug loading compared with the more conventional PH101 grade.
- Introducing small amounts of mesoporous silicon dioxide provided a positive impact to the manufacturing process.
- Process optimization especially during wet massing stage was also critical to the success of the final product.
Materials
Microcrystalline Cellulose (Avicel PH-101, Avicel PH-301), mesoporous silica (Syloid 244FP), Opadry QX