Comparison of the physical and chemical stability of niclosamide crystal forms in aqueous versus nonaqueous suspensions.
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 HA and HB, 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, HA, which was reasonably stable but which did eventually transform to the most stable monohydrate HB. The order in which these crystal forms transformed to monohydrate HB were: Anhydrate > N,N-dimethylformamide > dimethyl sulfoxide > methanol > tetraethylene glycol > monohydrate HA. 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.
de Villiers
Melgardt M
MM
Department of Basic Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe, Monroe, Louisiana 71209, USA devilliers@ulm.edu
Mahlatji
Mabatane D
MD
van Tonder
Elsa C
EC
Malan
Sarel F
SF
Lötter
Antonie P
AP
Liebenberg
Wilna
W
D000969:Antinematodal Agents / Q000737:chemistry*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003460:Crystallization; D004355:Drug Stability; D009534:Niclosamide / Q000737:chemistry*; D012995:Solubility; D013535:Suspensions; D013607:Tablets; D013696:Temperature; D014867:Water / Q000737:chemistry*
D000969:Antinematodal Agents; D013535:Suspensions; D013607:Tablets; D014867:Water; D009534:Niclosamide