Study On The Formation And Disintegration Mechanism Of Erythromycin Ethylsuccinate Gel-like Phase

Erythromycin ethylsuccinate(EES)is a widely clinic used erythromycin analog antibiotic,gelation phenomenon is quite common during its preparation process via solution crystallization,which has a bad influence on the crystallization operation.In this thesis,systematic study on the formation and disintegration mechanism of EES gellike phase was carried out.Properties characterizations including minimum gelation concentration measurements,rheological properties,thermally reversibility and microscale morphology characterization were performed on the gel-like phase of EES formed in acetone-water or 1-propanol,proving the supramolecular gel nature of the gelation products.Analysis of solvent parameters showed that moderate solvent polarity,which results in a biggish solubility of EES in the solvents,is an essential condition for gelation.The fibers inside the gel were crystalline and confirmed to be EES solvatomorphs that have never been reported before using powder X-ray diffraction(PXRD),thermal and composition analysis.The EES solvates own long fibrous crystal habit,which is apt to intertwine into a network microstructure to form the gel matrix.The gelation mechanism of EES was revealed by the analysis of solvent parameters,measurement of phase diagrams and spectral analysis.Through intermolecular hydrogen bonds,EES and solvent molecules assemble into lamellar gel structural units,and then form gel fibers via crystallographic mismatch branching growth.The fibers intertwine into a 3D network structure and immobilize the solution,giving birth to the gel at last.The reason for gelation lies in the formation of numerous fibrous solvates drove by the high degree of supersaturation,by controlling the degree of supersaturation the goal of preparing gels or avoiding gelation can be realized.ReactIR spectrometer was used to track the gelation of EES and disintegration of gels.It was found that the crystal habit transformation of EES solvates under shear force from fibrous to short straight needle-like,is one reason for the disintegration of gel.High performance liquid chromatography(HPLC)analysis indicated that,the decomposition of EES into erythromycin under longtime static inclosed condition leads to the dissolution of gel fibers,turning into the other reason for the disintegration of gel.