A novel co-processing method to manufacture an API for extended release formulation via formation of agglomerates of active ingredient and hydroxypropyl methylcellulose during crystallization

Abstract

A novel process for generating agglomerates of active pharmaceutical ingredient (API) and polymer by swelling the polymer in a water/organic mixture has been developed to address formulation issues resulting from a water sensitive, high drug load API with poor powder properties. Initially, the API is dissolved in water, following which hydroxypropyl methylcellulose (HPMC) is added, resulting in the imbibing of water, along with the dissolved API, into the HPMC matrix. The addition of acetone and isopropyl acetate (anti-solvents) then causes the API to crystallize inside and on the surface of HPMC agglomerates. The process was scaled up to 20 kg scale. The agglomerates of API and HPMC generated by this process are ∼350 µm diameter, robust, and have significantly better flow than the API as measured by Erweka flow testing. These agglomerates exhibit improved bulk density, acceptable chemical stability, and high compressibility. The agglomerates process well through roller compaction and tableting, with no flow or sticking issues. This process is potentially adaptable to other APIs with similar attributes.

Keywords:

• Co-process
• agglomerate
• flow
• extended release formulation
• crystallization

Acknowledgments

We gratefully acknowledge Shasad Sharif and Stevens Institute of Technology for their assistance with SEM and FIB-SEM and EDS.

Disclosure statement

No potential conflict of interest was reported by the authors.