Correlation between Hydrate Formation and the Physical Instability of Suspensions Prepared with Different Niclosamide Crystal Forms.

It is known that the properties and quality of many dosage forms depends on the physical properties of the drug powder, especially the crystal form of the drug. In this study the effects of polymorphism and pseudopolymorphism on the physical stability of niclosamide suspensions were studied. Through recrystallisation from organic solvents an anhydrated, monohydrated and three solvated crystal forms of niclosamide were prepared. The crystal forms were characterised by differential scanning calorimetry and thermogravimetric analysis. It was determined that the physical instability of aqueous niclosamide suspensions of these crystal forms depended on the transformation of the drug powder to a poorly water soluble monohydrate. Recommended approaches for the development of suspensions with these crystal forms are indicated and their application and pitfalls in suspension formulation are discussed.