Effect of natural polymer additives on crystal form and morphology of clozapine anhydrate and monohydrate

Natural polymer additives including ethyecellulose (EC), hydroxy propyl cellulose (HPC), hydroxypropyl methyl cellulose (HPMC), and sodium lignin sulfonate (SLS) were selected to modify the crystal form and morphology of clozapine crystals. The effects of cooling crystallization, anti-solvent crystallization and additives on clozapine crystal morphology were studied. The type of additive has an obvious effect on the morphology of crystal, while the dosage of additive has a great effect on the average particle size of crystal. Medicinal crystal form of clozapine anhydrate can be obtained after enhanced drying of clozapine monohydrate. Clozapine crystal particles with controllable crystal form, morphology and particle size can be prepared by anti-solvent crystallization method with additive. To further explore the mechanism of natural polymer additives on morphology regulation, molecular simulation was used to analyze the interaction between the main crystal surface, solvent and additives.