Physical Characteristics of Cilostazol–Hydroxybenzoic Acid Cocrystals Prepared Using a Spray Drying Method

Abstract

The cocrystal formation of pharmaceuticals can improve the various physical properties of drugs, such as solubility, without the need for chemical modification of the drug substances. In the present study, we prepared cocrystals of cilostazol and additive coformers (derivatives of hydroxybenzoic acid) using a spray drying method. Based on the preparation of the cocrystals of cilostazol and the coformers as reported previously, the characteristics of the cilostazol cocrystals prepared using solvent evaporation, slurry, and spray drying methods were compared. The physical characterization revealed that the spray drying method successfully produced cilostazol–4-hydroxybenzoic acid and cilostazol–2,4-dihydroxybenzoic acid cocrystals, whereas samples of cocrystals of cilostazol and 2,5-dihydroxybenzoic acid produced via the spray drying process appeared to contain coformer polymorphs. The dissolution of cilostazol was improved using the spray-dried cocrystal samples composed of coformers compared to samples prepared using cilostazol alone or a physical mixture. The present results provide useful information regarding the manufacture of cilostazol cocrystals and pharmaceutical cocrystals via spray drying in large-batch production.

Keywords

• cocrystal
• coformer
• spray drying
• cilostazol
• hydroxybenzoic acid