A new estra-1,3,5(10)-triene-3,17β-diol solvate: estradiol–methanol–water (3/2/1)

Abstract

The title solvate of the steroid 17beta-estradiol (E(2)) with methanol and water, C(18)H(24)O(2).0.67CH(4)O.0.33H(2)O, is the first E(2) derivative to contain three crystallographically independent molecules in the asymmetric unit. The three steroid molecules, along with two methanol molecules and a water molecule, create a three-dimensional hydrogen-bonded system. Three-sided columns are formed, with the estradiol molecules aligned lengthwise parallel to (101), and joined by solvent molecules at both hydrophilic ends. The three estradiol molecules differ slightly in their ring-bowing angles, i.e. the angle between the mean plane of the A ring and that of the BCD ring; this angle ranges from 7.1 to 12.2 degrees.

The solid state forms of the sex hormone 17-β-estradiol

“…While a good deal of crystallization space has been explored, it nevertheless remains likely that many other undiscovered solid forms may still be found, such as mixed solvates exemplified by (BES) 3 IJMeOH) 2 IJH 2 O) (WURWEL). 23 There are many more possibilities for multicomponent complexes such as that formed with urea (ESOURE10) 38 and recently, formamide. 39,40 The extension to co-crystallization with larger molecules has been partially in-vestigated, with cocrystals with isonicotinamide (ULUFIS) and piperazine dihydrate (ULUFOY) being reported from a search for increased solubility, 41 and with pyrene (CUTBEZ), phenanthrene (RUGYID), benzo[h]quinoline (RUFYIC) and 1,2-dimethylnapthalene (RUFOY) in investigations of the molecular recognition of steroids.…”

“…22 A mixed solvate (BES) 3 IJMeOH) 2 IJH 2 O) (WURWEL) has also been reported. 23 The most characteristic property of 17-β-estradiol is its tendency to crystallize as BES•0.5H 2 O, in which it precipitates not only from aqueous solution, but also from ethyl acetate, chloroform, absolute ethanol and other supposedly anhydrous solvents. 16 This may explain why the PXRD patterns presented 24 for four different solvate forms of 17-β-estradiol are so extremely similar to that for BES•0.5H 2 O that it is likely that only BES•0.5H 2 O was obtained in these cases.…”

Solid-state characterization of 17β-estradiol co-crystals presenting improved dissolution and bioavailability

“…17 Polymorphism of E2 has been comprehensively screened and four crystal forms, including two solvates and two polymorphs, were discovered. [18][19][20][21] Different oral formulation technologies of E2 have been employed to increase its solubility. To date, nanoparticles, 22 microemulsions, 23 and solid dispersions 24,25 have been reported.…”