Polymorphism and isostructurality of cyclodextrins and their inclusion complexes

Abstract

Broad classification of the crystal structures and packingmodes of cyclodextrins (CDs) and their inclusion complexes into channel and cage types is well known. An example of a more detailed classification is that for dimeric (-CD complexes [1] where channel-, intermediate channel-, screw channeland chessboard arrangements were identified. A survey of available CD inclusion complexes of organic guests led to their systematic classification into ∼17 isostructural series, each with a distinctive PXRDpattern [2]. These patterns have proven useful for definitive characterization of new inclusion complexes.More recently, several reports of polymorphs of CDs and their inclusion complexes have appeared, indicating yet wider structural diversity in this class of compounds. In this report, we review these aspects of CDs and their inclusion complexes, and present data for three crystalline forms of permethylated β-CD and several β-CD inclusion complexes of salts of the anti-inflammatory drug diclofenac and its structural isomer meclofenamic acid. The former series comprises a monohydrate (Form 1), a trihydrate (Form 2) and an anhydrate (Form 3), all crystallizing in the space group P212121. The latter two phases are isostructural and were obtained during failed attempts to obtain inclusion complexes with the drugs bucetin and atenolol [3]. The most striking feature revealed here is the relatively round shape of the host molecule in Forms 2 and 3 that results from inclusion of two primary methoxyl groups of each host into the cavity of a neighbouring CD molecule. This contrasts strongly with the collapsed structure of the host in Form 1, where one of the seven methylated glucose rings was found to adopt the unusual C4 conformation. The β-CD complexes of diclofenac prepared and characterized in our laboratory include those of the sodium, potassium and caesium salts of the drug. Although the mode of inclusion of the drug anion in the host cavity is essentially the same in this series, only the latter two complexes are isostructural, crystallizing in the space group P212121, while the crystal of the sodium analogue is hexagonal, space group P61. We recently prepared the Ca 2+ and Mg salts of both diclofenac andmeclofenamic acid, and attempted their inclusion in β-CD. Surprisingly, no complex formation was detected with either of the salts of diclofenac, but its isomer yielded isostructural crystals with compositions β-CDc(meclofenamate) (M)0.5(17H2O. These were found to be isostructural with the sodium analogue investigated earlier and in all three complexes a common mode of inclusion of the guest is observed. New instances of isostructurality among CDhosts and their inclusion complexes reported here have been incorporated into an updated library which includes their PXRD patterns.