(204o) Solid Form Transformation of Disodium Guanosine 5?-Monophosphate: Thermodynamic Perspective

Disodium guanosine 5′-monophosphate (5′-GMPNa₂) is one of the four common ribonucleotides that constitute ribonucleic acids (RNAs), containing pentose phosphate and amidogen groups, which is widely used in food, pharmaceutical and fine chemistry and other industries. The mainly solid forms of 5′-GMPNa₂ are amorphous form and crystal polymorphs (I, II, III and IV-form), among all the solid forms, the I-form and amorphous form are the common forms. However amorphous form is often prepared during crystallization process with immature processing conditions, while the crystal products is with poor quality. Some researches have reported that the amorphous form of 5′-GMPNa₂ can transform to crystal form with the driving force of solubility difference of the two different forms. Hence the solubility of polymorphous of 5′-GMPNa₂ is extremely significant for control course of crystallization and study mechanism of polymorphous transformation. In this work, we are trying to elaborate the transformation mechanism of 5′-GMPNa₂ between amorphous form and crystal form from thermodynamic perspective.

A series of means (TG-DSC, PXRD, SEM) were employed to characterize 5′-GMPNa₂, and to prove that the different solid form of experimental materials are different in thermodynamic properties, structure arrangement and crystal habit. The solubility of crystalline and amorphous form of 5′-GMPNa₂ in binary isopropanol-water and ethanol-water solvent mixture with the temperature ranging from 298.15 K to 318.15 K and pH ranging from 8.5 to 10.0 were studied, meanwhile the residual solids were measured by PXRD and SEM. The solubility data shows that 5′-GMPNa₂ is more soluble in ethanol than isopropanol at same mole fraction and temperature, mainly because that 5′-GMPNa₂ is polyhydroxy compound，which can easily dissolve in solvent with larger polarity. The PXRD together with solubility data indicates that the transformation of solid forms 5′-GMPNa₂ is existed during the solubility experiment but have different direction in different solution environment. In isopropanol - water system, crystalline form can transform to amorphous under the high temperature and low proportion isopropanol, while amorphous form has the tendency to transform to crystalline form under the low temperature and high proportion isopropanol with thermodynamic viewpoint; However in ethanol - water system, amorphous form can transform spontaneously to crystalline form when ethanol proportion great than or equal to 20%, in addition amorphous form has the tendency to transform to crystalline when ethanol proportion less than or equal to 10% with thermodynamic viewpoint theoretically.

Reasons for transformation of 5′-GMPNa₂ in different solvent environment can summarize as the different adsorption capacity of solvent between 5′-GMPNa₂ contributes different direction of structure rearrangement. Since adsorption capacity between 5′-GMPNa₂ and ethanol is more stronger than isopropanol_, so isopropanol is more easily dropped out from 5′-GMPNa₂ than ethanol during the formative process of 5′-GMPNa₂ cluster, which results that clusters have large disordering in isopropanol and need more time to rearrange in isopropanol. That’s why that crystalline form transform to amorphous form in isopropanol-water system, while crystalline form transform to amorphous from in ethanol-water system during the solubility experiment process.