Yıkama Metodu Kullanılarak Saflaştırılan Amoksisilin Trihidratın Taguchi Yöntemi ile Optimizasyonu

Yıl 2022, Cilt: 12 Sayı: 2, 933 - 945, 01.06.2022

Mustafa Ergin

https://doi.org/10.21597/jist.1065147

Cited By: 2

Öz

Saf bir kristal ürün elde etmek için tekrar tekrar uygulanan kristalizasyon basamakları veya farklı kimyasallara başvurulması, bitmiş ürünün veriminde farklı sorunlara neden olabilir. Bundan dolayı, kristal ağın içerisindeki safsızlıklar, ana ürünü etkilemeden uzaklaştırılmalıdır. Bu çalışmada, Amoksisilin trihidrat (Amct) ve safsızlık olarak 4-hidroksifenilglisin (4-HPG) kullanılmıştır. Amct kristal kafesinden, safsızlık olarak 4-HPG’nin yıkama yöntemleri kullanılarak uzaklaştırılması gösterilmiştir. Ayrıca, bu çalışmada ilk kez, yıkama verimi ile yıkama yöntemleri, çözeltiler ve sıcaklıklar arasındaki ilişkiyi incelemek için Taguchi metodu kullanılmıştır. Denemelerde bir Büchner cam hunisi istenilen sıcaklıkta ve ürün kaybı olmadan çalışılacak şekilde yeniden tasarlanmıştır ve denemeler burada yapılmıştır. Bu çalışma, farklı yıkama yöntemleri, kullanılan Taguchi metot ve yeniden tasarlanan Büchner cam hunisi ile literatüre farklılık katmaktadır. Etki grafiklerinden yıkama verim değerlerini etkileyen faktörler sırasıyla yıkama yöntemi, sıcaklık ve çözelti olarak belirlenmiştir. En yüksek verim, tek aşamalı yıkama yöntemi ile Etilalkol kullanılarak 15°C’de elde edilmiştir.

Anahtar Kelimeler

Amoksisillin trihidrat, 4-hidroksifenilglisin, kristalizasyon, saflandırma, Taguchi metot

Optimization of Amoxicillin Trihydrate Purified Using Washing Method by Taguchi Method

Öz

Repeated crystallization operations or the employment of several chemicals to achieve a pure crystalline product might result in a variety of issues with the completed product's yield. As a result, the impurities in the crystal mesh must be eliminated while the core product remains unaffected. Amoxicillin trihydrate (Amct) and 4-hydroxyphenylglycine (4-HPG) were employed as impurities in this investigation. Washing methods were proven to be effective in removing 4-HPG contaminants from the Amct crystal lattice. In addition, for the first time in this study, the Taguchi technique was employed to investigate the link between yield and washing procedures, solutions, and temperatures. A Büchner glass funnel was developed in the experiments to work at the required temperature with no product loss, and testing were undertaken here. This study makes a difference to the literature with different washing methods, the Taguchi method used and the redesigned Büchner glass funnel. From the effect graphs, it was determined that the factors affecting the yield values were washing method, temperature and solution, respectively. The highest washing yield was obtained at 15°C by using ethanol with the one-stage washing method.

Anahtar Kelimeler

Amoxicillin trihydrate, 4-hydroxyphenylglycine, crystallization, purification, Taguchi method

Kaynakça

• Alemzadeh I, Borghei G, Vafi L, Roostaazad R, 2010. Enzymatic synthesis of amoxicillin with ımmobilized penicillin g acylase. Scientia Iranica. (Transaction C, Chemistry, Chemical Engineering), 17: 106-113.
• Alvarez AJ, Myerson AS, 2010. Continuous plug flow crystallization of pharmaceutical compounds. Crystal Growth, 10: 2219-2228.
• Bezerra I, Chiavone-Filho O, Mattedi S, 2013. Solid-liquid equilibrium data of amoxicillin and hydroxyphenylglycine in aqueous media. Brazilian Journal of Chemical Engineering, 30: 45-54.
• Bruggink A, Roos EC, de Vroom E, 1998. Penicillin acylase in the industrial production of β-lactam antibiotics. Organic Process Research & Development, 2(2): 128-133.
• Diender MB, Straathof AJJ, Van Der Does T, Ras C, Heijnen JJ, 2002. Equilibrium modeling of extractive enzymatic hydrolysis of penicillin g with concomitant 6‐aminopenicillanic acid crystallization. Biotechnology and bioengineering, 78(4): 395-402.
• Douhéret G, Davis MI, Reis JCR, Blandamer MJ, 2001. Isentropic compressibilities—experimental origin and the quest for their rigorous estimation ın thermodynamically ıdeal liquid mixtures. ChemPhysChem, 2: 148-161.
• Elander RP, 2003. Industrial production of β-lactam antibiotics. Applied Microbiology and Biotechnology, 61: 385-392.
• Engel J, Kleemann A, Kutscher B, Reichert D, 2014. Pharmaceutical Substances, 2009: Syntheses, Patents and Applications of the Most Relevant APIs. Georg Thieme Verlag.
• Ergin A, Ergin MF, 2021. The role of antifouling coating in the marine industry. Research & Reviews in Engineering, 53.
• Ergin MF, 2021. Purification of amoxicillin trihydrate in the presence of degradation products by different washing methods. CrystEngComm, 23(46), 8121-8130.
• FDA, 2021. Drug Shortages [Online]. Https://Www.Fda.Gov/Drugs/Drug-Safety-And-Availability/Drug-Shortages. [Accessed].
• Franks F, 2013. Water in crystalline hydrates aqueous solutions of simple nonelectrolytes (Vol. 2), Springer Science & Business Media.
• Giron D, Goldbronn C, Mutz M, Pfeffer S, Piechon P, Schwab P, 2002. Solid state characterizations of pharmaceutical hydrates. Journal of thermal analysis and calorimetry, 68: 453-465.
• Hsi KHY, Concepcion AJ, Kenny M, Magzoub AA, Myerson ASJC, 2013. Purification of amoxicillin trihydrate by impurity-coformer complexation in solution. CrystEngComm, 15: 6776-6781.
• Kıvak T, 2014. Optimization of surface roughness and flank wear using the Taguchi method in milling of Hadfield steel with PVD and CVD coated inserts. Measurement, 50: 19-28.
• Klein EY, Van Boeckel TP, Martinez EM, Pant S, Gandra S, Levin SA, Goossens H, Laxminarayan R, 2018. Global Increase and Geographic Convergence in Antibiotic Consumption Between 2000 and 2015. Proceedings of the National Academy of Sciences, 115: E3463-E3470.
• Kumar KK, Choudhury S, 2008. Investigation of tool wear and cutting force in cryogenic machining using design of experiments. Journal of Materials Processing Technology, 203: 95-101. Lin C, 2004. Use of the Taguchi method and grey relational analysis to optimize turning operations with multiple performance characteristics. Materials And Manufacturing Processes, 19: 209-220.
• Onar HÇ, Vardar BA, 2018. Synthesis and antioxidant activity of novel 8-formyl-4-substitued coumarins. Bulletin of the Chemical Society of Ethiopia, 32: 175-178.
• World Health Organization (WHO), 2018. Who Report On Surveillance Of Antibiotic Consumption: 2016-2018 Early Implementation.
• Rudolph ESJ, Zomerdijk M, Ottens M, Van Der Wielen LAM, 2001. Solubilities and partition coefficients of semi-synthetic antibiotics in water+ 1-butanol systems. Industrial & Engineering Chemistry Research, 40: 398-406.
• Vartak S, Myerson AS, 2017. Continuous crystallization with impurity complexation and nanofiltration recycle. Organic Process Research & Development, 21: 253-261.
• Yaşa H, 2020. A Study On Catalyst Used In Mannich Reaction To Obtain Β-Amino Carbonyl Compounds In Recent Years. Theory Research In Science Mathematics II, 73.
• Yaşa H, Ergin MF, Ergin A, Alkan G, 2016. Importance of inert gases for chemical transportation. Proceedings Book, 825.
• Youshko MI, Moody HM, Bukhanov AL, Boosten WH, Švedas VK, 2004. Penicillin acylase‐catalyzed synthesis of β‐lactam antibiotics in highly condensed aqueous systems: Beneficial impact of kinetic substrate supersaturation: Beneficial impact of kinetic substrate supersaturation. Biotechnology and Bioengineering, 85: 323-329.