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