Purification of amoxicillin trihydrate in the presence of degradation products by different washing methods

ERGİN, Mustafa

doi:10.1039/d1ce01073e

Cited by 6 publications

(5 citation statements)

References 37 publications

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“…To standardize the crystallization process, a 100 mL Büchner glass funnel and two 100 mL jacketed reactors were utilized in the experiments. The Büchner glass funnel employed in this study was specially designed to minimize crystal loss, and all experiments were conducted using this apparatus. , The process temperature and the temperatures of all solutions used were adjusted to room temperature. Prior to each experiment, the system was operated under the specified conditions for 30 min to attain a stable state.…”

Section: Methodsmentioning

confidence: 99%

“…The literature predominantly focuses on the adverse impact of introducing impurities structurally similar to the primary molecule on crystal growth. The separation of AMCT from its own degradation products, in particular, has garnered emphasis. − In their investigation, Feng et al demonstrated that an increase in the concentration of degradation products leads to a decrease in AMCT nucleation . In another study, Ghassempur et al detailed the integration of impurities into the AMCT crystal lattice and its consequent impact on the process.…”

Section: Introductionmentioning

confidence: 99%

“…Similar to other β-lactam antibiotic drugs, the crystallization of amoxicillin trihydrate (AMCT) also plays a crucial role in controlling the crystalline form, shape, and size. Affordable, widely available, and highly efficient acids such as hydrochloric acid (HCl), sulfuric acid (H 2 SO 4 ), and glacial acetic acid (CH 3 COOH) are the most commonly used acids in the purification of AMCT. − ,− However, using these acids raises several environmental, health, and safety concerns due to their extreme corrosiveness and respiratory hazards . In this study, the utilization of citric acid, a natural organic acid, was explored as an alternative to these acids for the purification of amoxicillin.…”

Section: Introductionmentioning

confidence: 99%

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Investigating the Role of Citric Acid as a Natural Acid on the Crystallization of Amoxicillin Trihydrate

Celik Onar,

Ergin,

Yasa

2023

ACS Omega

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This study investigates the use of environmentally friendly citric acid as the main player in the process, rather than as an additive, to remove impurities from amoxicillin trihydrate (AMCT) crystals, aiming to optimize their purity and yield. By manipulating the concentration of citric acid, mixing speed, crystallization time, and pH, the researchers conducted experiments using a full factorial design. The dissolution stage was analyzed in both batch and continuous crystallization processes, emphasizing the significance of citric acid in enhancing crystallization. HPLC analyses were performed on the resulting crystals, and the data were analyzed using the Multi-Vari Chart program. The findings demonstrated that higher citric acid concentrations positively affected the yield, while factors such as crystallization time, mixing speed, and pH also contributed to the increased yield. The crystals obtained exhibited desirable dimensions sought after in the pharmaceutical industry, eliminating the need for additional purification steps. This study showcased the potential of citric acid in AMCT crystallization, offering advantages in product design, purification, and synthesis. The optimized conditions included a citric acid concentration of 2.0 M, mixing speed of 1000 rpm, crystallization time of 120 min, and pH of 5.5. Notably, the developed process proved to be environmentally friendly by avoiding the use of harmful chemicals, serving as a green alternative for crystallization processes, and producing purer AMCT products. Overall, this research contributes to the existing literature by highlighting the efficacy of citric acid in impurity removal and the optimization of AMCT crystal purity and yield.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Investigating the Role of Citric Acid as a Natural Acid on the Crystallization of Amoxicillin Trihydrate

Celik Onar,

Ergin,

Yasa

2023

ACS Omega

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“…The synthesis of xanthenes, especially thioxanthenes, has increased remarkably in recent years due to their wide range of biological and pharmacological properties. As an example of its biological and pharmacological properties, anticancer, − antitumor, − antiviral, antimicrobial, − antibacterial, − and anti-inflammatory activities can be cited. Moreover, some types are also used as materials in dye technology, , sensor, , and organic light-emitting diodes (OLEDs) − due to the conjugation and heteroring in their structures, ensuring optical and electrochemical properties.…”

Section: Introductionmentioning

confidence: 99%

Intramolecular Friedel–Crafts Reaction with Trifluoroacetic Acid: Synthesizing Some New Functionalized 9-Aryl/Alkyl Thioxanthenes

Deniz,

Yıldız,

Başpınar Küçük

2024

ACS Omega

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In this study, a series of halogen-substituted thioxanthenes were synthesized because the most important and biologically active derivatives of xanthenes are thioxanthenes. In order to obtain new thioxanthene derivatives, first, the starting molecules were synthesized by the appropriate reaction methods in two steps. The intramolecular Friedel−Crafts alkylation (FCA) method was used to convert the prepared three aromatic substituted starting alcohol compounds to their corresponding thioxanthenes by cyclization. For the intramolecular FCA reaction of secondary alcohols, which are the starting compounds (1a−1t), organic Bro̷ nsted acids, which require more innovative, easier, and suitable reaction conditions, were used instead of halide reagents with corrosive effects as classical FCA catalysts. Trifluoroacetic acid was determined to be the organocatalyst with the best yield. Therefore, some original 9-aryl/alkyl thioxanthene derivatives (2a−2t) were synthesized using the optimized FCA method. In addition, a new sulfone derivative of thioxanthene 3i was prepared by performing the oxidation reaction with one of the obtained new thioxanthene 2i. Thioxanthenes and their derivatives are important heterocyclic structures that contain pharmacologically valuable sulfur and are used in the treatment of psychotic diseases such as Alzheimer's or schizophrenia, as well as a number of potent biological activities.

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“…Therefore, it is very important that these impurities can be easily and cheaply identified and removed. For this, the impurities were tried to be removed with the washing process [12], and different chemicals [13,14].…”

Section: Introductionmentioning

confidence: 99%

Determination of amoxicillin trihydrate impurities 4-hydroxyphenylglycine (4-HPG) and 6-Aminopenicylanic acid (6-APA) by means of ultraviolet spectroscopy

ERGİN¹,

Yaşa²

2022

Methods Appl. Fluoresc.

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Amoxicillin is one of the broad-spectrum β-lactam antibiotics widely used in the treatment of many diseases. It is inevitable that 4-hydroxyphenylglycine (4-HPG) and 6-Aminopenicylanic acid (6-APA), which are used during the production of this antibiotic, are incorporated into the molecular lattice of the product as impurities. Today, many expensive methods and chemical devices are used for the purification of Amoxicillin by determining 6-APA and 4-HPG, which are defined as impurities. In this study, it was aimed to develop a fast, simple, and specific UV-spectrophotometric method for the determination of 4-HPG and 6-APA. Another aim of this article is to cause as little harm as possible to the environment and human health by using as few chemicals as possible throughout the study. In this study, all attempts to determine 6-APA and 4-HPG, which are impurities in the production of amoxicillin, were carried out with the help of a UV/VIS spectrophotometer. Also, Four different concentrations of NaOH were used as a solvent for each impurity. UV spectra of 4-HPG and 6-APA concentrations between 210 and 400 nm were measured. In the literature, the UV spectrum of 4-HPG has been revealed for the first time in this study and examined in detail. The UV spectrum of 4-HPG was characterized in 3 regions. Again, the response of 6-APA to different NaOH concentrations was demonstrated for the first time in this study. It was determined that the peaks of 6-APA dissolved in NaOH shifted from 222 nm to 227 nm depending on the concentration amount. In addition, it is an ideal green procedure that makes a difference in the literature, as the study is carried out for the control and determination of impurities without the use of any organic solvents or chemicals harmful to the environment.

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Purification of amoxicillin trihydrate in the presence of degradation products by different washing methods

Abstract: Repeated crystallization or the use of different chemicals to obtain a pure crystal can cause yield/purity issues. Therefore, impurity penetrating the crystalline mesh should be removed as much as possible...

Cited by 6 publications

References 37 publications

Investigating the Role of Citric Acid as a Natural Acid on the Crystallization of Amoxicillin Trihydrate

Investigating the Role of Citric Acid as a Natural Acid on the Crystallization of Amoxicillin Trihydrate

Intramolecular Friedel–Crafts Reaction with Trifluoroacetic Acid: Synthesizing Some New Functionalized 9-Aryl/Alkyl Thioxanthenes

Determination of amoxicillin trihydrate impurities 4-hydroxyphenylglycine (4-HPG) and 6-Aminopenicylanic acid (6-APA) by means of ultraviolet spectroscopy

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