Comparison of the Physical and Chemical Stability of Niclosamide Crystal Forms in Aqueous Versus Nonaqueous Suspensions

Abstract

In an effort to produce physically stable and pharmaceutically acceptable suspensions of niclosamide, this study reports the differences in physical and chemical stability of aqueous vs. nonaqueous suspensions of a niclosamide anhydrate, two monohydrates H_A and H_B, a 1:1 niclosamide N,N‐dimethylformamide solvate, a 1:1 niclosamide dimethyl sulfoxide solvate, a 1:1 niclosamide methanol solvate, and a 2:1 niclosamide tetraethylene glycol hemisolvate. Evaluation of aqueous and nonaqueous suspensions showed that in aqueous suspensions anhydrous, and solvated niclosamide crystal forms were transformed to a monohydrate, H_A, which was reasonably stable but which did eventually transform to the most stable monohydrate H_B. The order in which these crystal forms transformed to monohydrate H_B were: Anhydrate > N,N‐dimethylformamide > dimethyl sulfoxide > methanol > tetraethylene glycol > monohydrate H_A. In a nonaqueous propylene glycol vehicle, the transformation to the monohydrous forms was not observed and on desolvation the solvated crystals transformed to the anhydrous form. In all cases, immediately upon desolvation or dehydration, the crystal structures of the desolvated materials were similar to that of the solvated materials. However, the isomorphic structures, formed after desolvation, were unstable and rehydrated or resolvated when exposed to the solvent or converted to the anhydrous form in a dry environment. The crystal forms remained chemically stable in both aqueous and nonaqueous suspensions for the length of the study.

Key Words:

• Niclosamide
• Polymorphs
• Suspensions
• Aqueous vehicle
• Nonaqueous vehicle