(651c) A Quick Design of Spherical Agglomeration of Cefotaxime Sodium Based on Adhesion Free Energy

Spherical crystallization could transform the microcrystalline drug itself into spherical agglomerates improving flowability, compressibility, mean size and compactibility of the drug. Solvent system for spherical crystallization is significant. However, much of the work concerning on the design of wetting liquid was conducted by trials and errors, wasting time and energy. Therefore, this work reports a method to select the proper wetting liquid for spherical agglomeration of cefotaxime sodium by combining theoretical prediction and experimental validation. The theoretical prediction is achieved by calculating the adhesion free energy between the solid surfaces and the liquid (solvents). Various solvents have been screened and candidates with a negative adhesion free energy such as water and chloroform are selected for spherical agglomeration experiments. Experimental results also validate that water and chloroform can be acted as the wetting liquid to form spherical agglomerates of cefotaxime sodium, but mixtures of them can produce high-quality spherical agglomerates. The size distribution, morphology, cohesion and compactibility of the agglomerates have been characterized in terms of process variables such as agitation speed and temperature. An agitation speed of 200 rpm and a temperature of 297.15 K are found to give the optimal result. Finally, the spherical agglomeration process is visualized by PVM and a possible agglomeration mechanism is proposed.