Gelation Mechanism of Erythromycin Ethylsuccinate During Crystallization

Su, Xiandong; Gao, Zhenguo; Bao, Ying; Guan, Miao; Rohani, Sohrab; Yin, Qiuxiang; Hao, Hongxun; Xie, Chuang; Wang, Jingkang

doi:10.1007/s12209-018-0163-5

Cited by 5 publications

(5 citation statements)

References 22 publications

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“…Additionally, gelation phenomenon cannot happen in all solvents; choosing the suitable solvents can prevent or promote this phenomenon in practical production [14]. Under the gel temperature, several parameters, such as Hansen solubility parameters, Kamlet-Taft parameters, and Hildebrandt solubility parameters [15][16][17], can be introduced to characterize the solvent properties and indicate the gelation tendency of a gelator.…”

Section: Mechanism Of the Gel-crystal Transitionmentioning

confidence: 99%

Gelation Phenomenon During Crystallization of Cefpiramide Sodium

Yin

Guo

et al. 2019

Trans. Tianjin Univ.

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Unlike the adverse effect caused by the gelation during crystallization process, gelation of cefpiramide sodium was found to provide ideal product properties, such as a larger and more regular crystal shape. The causes of the gelation phenomenon and the mechanism of gel-crystal transition during the crystallization of cefpiramide sodium were both investigated in this work. The gel was formed due to the strapping of the solvents by the networks of cefpiramide sodium molecules. The whole gel-crystal transition process was divided into the following three stages: (1) when the temperature decreased, the system reached a metastable-state gelation; (2) the initial microcrystal in the gel grew slowly because of the low supersaturation; and (3) the gel finally disappeared, and a larger and more regular crystal was formed. The Hansen solubility parameters were used to analyze the effects of the solvents on this gelation; the analysis results can serve as guidance for solvent screening in the actual production process.

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Section: Mechanism Of the Gel-crystal Transitionmentioning

confidence: 99%

Gelation Phenomenon During Crystallization of Cefpiramide Sodium

Yin

Guo

et al. 2019

Trans. Tianjin Univ.

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“…It is found that the gelation phenomenon often occurs in the crystallization process of tilmicosin phosphate, which leads to small particle sizes and easy aggregation. In recent years, there have been reports on the gelation phenomenon and gelation mechanism in the process of drug crystallization. − Ouyang et al studied the gel formation and spontaneous crystallization of Valnemulin hydrogen tartrate in a mixed solvent system. The results showed that the gel was formed temporarily and played an intermediate role in the amorphous transformation process.…”

Section: Introductionmentioning

confidence: 99%

Gelation Phenomenon and Its Regulation Strategy of Tilmicosin Phosphate

Rong,

Hao,

Wang

et al. 2024

Crystal Growth & Design

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Amorphous tilmicosin phosphate (TMP) suffers from low stability, and its crystalline product is not reported. At the same time, the gelation phenomenon often occurs in the crystallization process of TMP, which seriously affects the robustness of the process and product quality. In this paper, a crystal form of TMP was developed, and it was determined to be tilmicosin phosphate trihydrate by powder X-ray diffraction, thermogravimetric differential scanning calorimetry, Fourier transform infrared (FTIR), and Karl Fischer water content test. Besides, the gelation phenomenon and the gel transition process during TMP crystallization were studied by spectroscopic and microscopic methods. The results show that TMP gel is an intermediate form formed by amorphous TMP and solvent, and the type of solvents and water content in these solvents were important factors affecting the gelation and crystallization behavior of TMP. Finally, the TMP crystallization process was optimized, and trihydrate of TMP could be obtained directly without passing through the intermediate gel state. It was found that, after process optimization, the particle size, crystallinity, and stability of the obtained crystal products were improved.

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“…There are a lot of studies that aim to solve the gelation phenomenon during a crystallization process. ,− Controlling the solution concentration and associated temperature is a common method to optimize the process to avoid gelation. ,,− And another method is seeding-assisted crystallization to initialize the nucleation to avoid gel phase formation. It can induce the crystallization process, and the crystal growing from the crystal nucleus can achieve product consistency, to improve the yield and quality of crystals.…”

Section: Introductionmentioning

confidence: 99%

“…Yin et al 24 Strong polar interactions between solvent molecules and carboxyl, amine, or acyl groups exposed on the surface of CTX crystals are key factors in forming gels. Su et al 25 studied the gelation mechanism of erythromycin ethylsuccinate (EES) in the crystallization process, and the results indicated that the fibers in the gelatinous phase were new EES solvates. It was concluded that, through intermolecular hydrogen bonds, EES and solvent molecules, through crystallography mismatch, nucleate growth and assemble into fibers.…”

Section: Introductionmentioning

confidence: 99%

Gelation Mechanism and Oscillatory Temperature Control Strategy in Perindopril Erbumine Solution Crystallization

Liao

Huang

Zhou

et al. 2023

Crystal Growth & Design

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The gelation phenomenon often occurs in the solution crystallization process, which would seriously affect the process robustness and product quality. In this paper, the gelation phenomenon during the solution crystallization of perindopril erbumine (PDP) was systematically studied by spectroscopy and microscopy techniques. The results suggest that the PDP gel does not have the characteristic diffraction peak of the PDP crystal and the infrared spectrum has changed significantly compared with that of the crystal product. Accordingly, the mechanism of the gelation phenomenon of PDP was inferred to follow the status of aggregates, amorphous, crystalline fibers, and jelly-like phases during the gelation process development. Based on the proposed gelation mechanism, three controlling strategies, namely, direct cooling crystallization, seeding-assisted crystallization, and oscillatory temperature crystallization, were carried out to evaluate the effectiveness of process optimization. Inspired by direct nucleation control theory, through controlling the seed crystal number before the cooling step, the oscillatory temperature crystallization strategy effectively avoided the gelation problem, and the crystal product has good filtration properties and powder properties, which provides a feasible process method for practical production, avoiding the gelation phenomenon and important changes of the production line.

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Gelation Mechanism of Erythromycin Ethylsuccinate During Crystallization

Cited by 5 publications

References 22 publications

Gelation Phenomenon During Crystallization of Cefpiramide Sodium

Gelation Phenomenon During Crystallization of Cefpiramide Sodium

Gelation Phenomenon and Its Regulation Strategy of Tilmicosin Phosphate

Gelation Mechanism and Oscillatory Temperature Control Strategy in Perindopril Erbumine Solution Crystallization

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