Geology

Oceanography

Engineering

Particle size

Composite material

Sphericity

Chemistry

Friability

Materials science

Ethyl cellulose

Cholesterol

Particle (ecology)

Gemfibrozil

Granulation

Chemical engineering

Chromatography

Polymer

Biochemistry

ACS Sustainable Chemistry & Engineering

Granulation is an important method to increase the fluidity of compounds, especially drugs with needle-like shapes. Another function of granulation is to mix active pharmaceutical ingredients (APIs) and excipients. In this research, oiling-out spherical agglomeration technology was used to obtain single- and multicomponent drug spherical particles of gemfibrozil, which can be directly compressed. This technology is carried out by simply heating and quenching operations in nonorganic solvents. Compared with the current granulation technology, it is estimated that approximately 400 metric tons (MT) of organic solvents per year can be saved for every 100 MT of gemfibrozil production. Meanwhile, based on the binary oiling-out phase diagram, the spherical particles of gemfibrozil were prepared with high bulk density (0.71 g cm–3), good sphericity (>80%), high yield (>95%), and adjustable particle size distribution, and the flowability is improved by 47.37%. Furthermore, the multicomponent functional particles of gemfibrozil and nimodipine for drug combination with the good morphology and uniform distribution of components were obtained by establishing ternary oiling-out phase diagrams. The results of tablet compaction showed a 4 times increase in tabletability from single-component spherical particles and a 2.7 times increase from multicomponent spherical particles compared to commercial powders. On the other hand, the failing case of gemfibrozil and simvastatin indicated that the binding energy between molecules is the key point of this method, and this result revealed the limitation of the oiling-out spherical agglomeration method for the current selection strategy of drugs. This work provided an experimental and theoretical basis for the further application of this green technology.

Design of Single and Multicomponent Drug Spherical Particles with Improved Powder Properties in Water Instead of Organic Solvents: A Case Study of Gemfibrozil