Solid Forms, Crystal Habits, and Solubility of Danthron

Abstract

The polymorphism, crystal habits, and solubility of 1,8-dihydroxyanthraquinone (danthron) were investigated in acetic acid, acetone, acetonitrile, nbutanol, and toluene. The solubility was determined for the commercially available form (FI) from 293.15 K to 318.15 K by the gravimetric method. The influence of solvents on crystal habit and polymorphic form has been investigated. Three different crystal habits of danthron were obtained from slow evaporation and cooling experiments. By evaporation, thin squares of FI were obtained from nbutanol and toluene solutions while both FI and fine needles of FII were obtained from acetone and acetonitrile solutions. In addition, needle-shaped solvate crystals were obtained from acetic acid solutions and the structure of the solvate was solved by single crystal X-ray diffraction. From cooling crystallization experiments, mixtures of FI and FII were often obtained from various solvents, but FI and FII possess distinct habits which can be easily distinguished by visual comparison. Slurry conversion experiments have established that FI is the thermodynamically stable polymorph of danthron at ambient conditions. Differntial scanning calorimetry (DSC) and high-temperature powder X-ray diffraction (PXRD) have shown that both FI and FII will transform into a high-temperature form (FIV) around 435 K to 439 K before this form melts at 468.5 K. FI, FII, and FIV have been characterized by transmission and high-temperature PXRD, scanning electron microscopy, infrared spectrometry, Raman spectrometry, thermogravimetric analysis, and DSC. The solubility of danthron FI in the pure organic solvents of the present work and in the temperature range investigated is below 4.3 % by weight and decreases in the order toluene, acetone, acetonitrile, and n-butanol.

The heterogeneous crystallization of a novel solvate of clozapine base in the presence of excipients

“…The solubility of CPB in MeOH was measured using the gravimetric method 37 in the range 5°C to 30°C, and the experimental set up was consistent with the method reported by Cheuk et al 38 The same method was applied to measure the solubility of CPB-MeOH solvate in methanol.…”

Simple multipurpose apparatus for solubility measurement of solid solutes in liquids

“…Literature survey shows that inexpensive simple apparatus for solubility measurement have been reported decades ago and had major limitations in terms of accuracy, throughput, and required large amount of solute (Butter, 1974;Harle et al, 2003;Knox, 1938;Schmitt and Grove, 1960). Moreover, most of the recent articles publishing solubility data measured by using classical isothermal technique Page 5 of 32 A c c e p t e d M a n u s c r i p t 5 lacks detailed schematic illustration of the equipment used for the measurements (Cheuk et al, 2015;Deng et al, 2015;Farjami and Jouyban, 2015;Shakeel et al, 2015;Y. Zhang et al, 2015).…”

Capturing the Role of Temperature and Entropy in Crystal Polymorphs Through Molecular Simulations

“…Properties than can change between polymorphs include density [11,20,31], compressibility [32], hardness [33,34], gel strength [35], flexibility [36], conductivity [26][27][28][29][30][37][38][39], explosivity [20,[22][23][24], catalytic activity [40,41], transparency [42,43], weather resistance [25,44], heat capacity [20], melting point [32,45,46], vapor pressure [46], stability [25,29], solubility [14,[47][48][49], bioavailability [14,33,48,[50][51][52][53][54], and dissolution rate [47,55,56].…”

“…Pharmaceutical researchers will typically search for alternate more-stable polymorph structures before mainstream production using a number of different screening techniques include slow cooling of the crystal in solution [29], slow evaporation of solvent [29], thermal annealing of known solid forms [29,75], as well as slurrying experiments [20,49,50,75,84] and Polymerinduced Heteronucleation [104].…”

“…In the next section, the process of experimentally searching for new solid forms is discussed. Solid forms can also be distinguished using thermogravimetric analysis [22,45,49], differential scanning calorimetry [14,45,48,49,53], as well as by examining the physical appearance such as color or crystalline shape [14,25,29,49,72]. Differential scanning calorimetry has the benefit of also providing key thermodynamic quantities such as heat capacities and enthalpies of transition between different forms.…”