Isomorphic desolvate

The chemical and physical stability of aqueous and nonaqueous suspensions of a number of solvatomorphs of niclosamide has been evaluated in an effort to develop pharmaceutically acceptable suspension formulations [90]. Studied in this work was the anhydrate, two polymorphic monohydrates, the 1 1, Y, A"-dimethyI I ormam ide solvatomorph, the 1 1 dimethyl sulfoxide solvatomorph, the 1 1 methanol solvato-morph, and the 2 1 tetraethylene glycol hemisolvate. All of the solvatomorphs were found to convert initially to one of the polymorphic monohydrates, and over time converted to the more stable monohydrate phase. The various solvatomorphs could be readily desolvated into isomorphic desolvates, but these were unstable and became re-hydrated or re-solvated upon exposure to the appropriate solvent. 

Isomorphic desolvates Substantial overlap of diffraction pattern (poorly distinguished) 0.5-2 Solvent resonances disappear. Drug resonances shift significantly relative to X-ray 0.5-5 Solvent bands disappear, chug bands shifted, highly similar to parent solvate spectra 5-10... 

FIGURE 6 Various possibilities that arise from dehydration of hydrate. A hydrate can dehydrate reversibly into various solid-state forms. It can dehydrate to form an anhydrous form of the drug or to a lower hydrate. Hydrate can also dehydrate to form an isomorphic desolvate where the crystal lattice is retained except for the absence of water. The crystal structure may also collapse on dehydration to form an amorphous form. Hydrates on dehydration can also result in different polymorphs. 

Detection of the solvent present in solvates and its interaction with the lattice (isomorphic desolvates). 

The solvate is poorly stable and the solvent is easily removed leading to either the original polymorphic form but creating a certain degree of disorder in the crystalline structure or to what is called a desolvate solvate form. In this last case, also named isomorphic desolvate , the desolvated solvate retains the structure of its parent solvated form. The X-ray diffraction patterns look similar between the parent and the daughter forms. In this situation we have the creation of a molecular vacuum which could substantially impact on the stability, hygroscopicity and mechanical characteristics of the DS and finally of the DP. 

Studies of the desolvation of solvatomorphs can be conducted using VT-XRPD. For instance, after the dehydration of a hydrate phase, one may obtain either a crystalline anhydrate phase or an amorphous phase and the XRPD pattern will clearly indicate the difference. In addition, should one encounter an equivalence in powder patterns between the hydrate phase and its dehydrated form, this would indicate the existence of channel-type water (as opposed to lattice boimd water). In one study, the solid-state properties of the isomorphic desolvates of cephalexin, cefaclor, erythromycin A, and spirapril hydrochloride were investigated, with the hygroscopicity of the compounds being evaluated using a vacuum moisture balance and the structural relaxation measured using a combination of VT-XRPD and isothermal microcalorimetry. " ... 

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