Exploration and investigation of various solid forms of an anti-glaucoma drug – dichlorphenamide

Abstract

Diclofenamide (or dichlorphenamide (DCF)) is a sulfonamide and a carbonic anhydrase inhibitor of the meta-disulfamoylbenzene class. It is used for treatment of acute angle closure glaucoma. However, its weak solubility and slow rate of dissolution restrict its therapeutic applicability. A complete solid-state screening experiment was carried out in order to discover some new forms with useful physicochemical properties. As a result, two polymorphic (forms II and III) and one dioxane solvated structure (DCF·dioxane) were obtained under different crystallisation conditions. These solid forms were characterized by powder X-ray diffraction (PXRD), single crystal X-ray diffraction (SCXRD), field emission scanning electron microscopy (FE-SEM), thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). Variable-temperature PXRD (VT-PXRD) and various solvent media were used to test the relative stability of the newly produced solid forms. Most of the forms remained stable at higher temperatures, but DCF·dioxane changed to form III. A similar trend was also seen in various solvent environments but in this case DCF·dioxane transformed to form II. Additionally, the physicochemical characteristics of these three polymorphs were extensively described, and the solubility was assessed in pH 1.2 and pH 6.4 media. All of the forms exhibited greater water solubility as compared to the parent DCF. Thus, we anticipate that the current findings will provide some insight to consider prior to the formulation of the DCF drug.