Spherical Crystallization of Mefenamic Acid

*To whom all correspondence should be addressed. he quality of a solid pharmaceutical preparation is influenced by primary micromeritic characteristics such as the shape and size of drug crystals, especially when large amounts of poorly soluble drugs are formulated. To improve the dissolution rate of poorly soluble drugs, fine crystals are preferred over large crystals because they provide a greater surface area. However, micronization can change drugpowder properties such as wettability, compressibility, packability, and flow and thus prevent efficient powder packaging. For that reason, it is more beneficial to transform the microcrystalline drug itself into an agglomerated form using a crystallization process. The resulting spherically agglomerated crystals then can be prepared in tablet form or compounded directly into a pharmaceutical system without further processing such as granulation. This approach also eliminates steps in the tableting process by making it possible to use direct tableting. Direct tableting, in which powders are simply mixed and compressed, generally is preferred because it saves time and reduces cost in comparison with the granulation technique. Flowability is an important characteristic for materials to be compressed as tablets. Spheres are the ideal physical shape for this purpose because they reduce the amount of contact with the walls of the machine parts. The spherical crystallization technique also involves the use of a bridging liquid that improves compressibility by acting as granulating fluid. Thus spherical crystallization is a method that helps achieve good flowability and compressibility. Spherical crystallization can be achieved by various methods such as simple spherical crystallization, emulsion solvent diffusion, ammonia diffusion, and neutralization (1,2). In this study the ammonia diffusion method was used, in which acetone, used as a solvent, enters a droplet of ammonia water and ammonia is liberated from the acetone–ammonia water– chloroform system (3). The three stages of the crystallization process are shown in Figure 1. First, the drug dissolved in ammonia water is precipitated while the droplets collect the crystals (Figure 1a). Simultaneously, ammonia in the agglomerate diffuses to the outer organic solvent (Figure 1b). Its ability to act as a bridging liquid weakens and subsequently spherical agglomerates are formed (Figure 1c). The drug mefenamic acid (MA) was selected for this study because it is poorly compressible, requires a high dose, and is poorly soluble in water. The aim of this study was to prepare spherical crystals of MA A U T H O R S