Chromatographic Separation of Bupivacaine Enantiomers by HPLC: Parameters Estimation of Equilibrium and Mass Transfer Under Linear Conditions

Silva, Ivanildo José da; Veredas, Vinícius de; Carpes, Marcos José Souza; Santana, César Costapinto

doi:10.1007/s10450-005-4903-1

Cited by 19 publications

(11 citation statements)

References 22 publications

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“…Furthermore, there is an evident influence of temperature on HETP, which decreases with increasing temperature from 25°C to 40°C. Other authors observed the same behavior while studying adsorption of enantiomers and sugars [12,20]. The increasing trend of HETP with velocity suggests that axial dispersion and mass transfer resistance control the column efficiency.…”

Section: Kinetic Data Of Amoxicillin Adsorption Onmentioning

confidence: 49%

Activated Carbon Adsorbent for the Aqueous Phase Adsorption of Amoxicillin in a Fixed Bed

et al. 2010

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Equilibrium constant and mass transfer parameters are needed for the study of amoxicillin separation in any process involving adsorption in fixed beds. In this work, the adsorption of amoxicillin and 6-aminopenillanic acid in aqueous solution on activated carbon were studied using static adsorption tests. The adsorption capacity was found to be strongly dependent on the pH of the aqueous phase. The adsorption constants, overall mass transfer coefficients, and axial dispersion coefficients for amoxicillin and 6-aminopenillanic acid were determined, by moment analysis, from a series of step tests in a fixed bed packed with activated carbon. The total bed voidage and axial dispersion coefficient were estimated from blue dextran pulse test data at different flow rates. The results show that adsorption intensity increased with increasing temperature. Furthermore, the increasing trend of HETP with velocity suggests that axial dispersion and mass transfer resistance control the column efficiency. IntroductionAmoxicillin, with molecular dimensions of 15.622 Å × 18.785 Å × 6.645 Å [1], is one of the major b-lactam antibiotics due to its high spectrum of activity, high solubility, high rate of absorption, and its stability under acid conditions. In the industry, the majority of semisynthetic b-lactam antibiotics are prepared by chemical methods. These reactions typically involve costly steps such as subzero degree Celsius conditions (-30°C), and toxic organic solvents like methylene chloride and silylation reagents [2]. Therefore, the enzymatic synthesis of semisynthetic antibiotics is an interesting industrial process, since it reduces the number of reaction steps and decreases the amount and toxicity of waste products per kilogram of antibiotic [3]. However, in the enzymatic production of amoxicillin at 25°C and pH 6.5, when the maximum yield of antibiotic production is achieved, the reaction media is composed of the desired product (the antibiotic), undesired products (resultant from hydrolysis), and unreacted substrates. The recovery of these biomolecules from bioreactors may involve several methods of extraction and purification, playing an important role in the global economic productive analysis of the process [4]. Adsorption is often used in downstream processing using various interactions, e.g., ionic, hydrophobic, affinity, etc., for the recovery of biomolecules, namely antibiotics [5]. Activated carbon and synthetic adsorbents have been used to remove biomolecules in the liquid phase [6][7][8], but no information is available on amoxicillin. Therefore, the purpose of this work is to study the separation of amoxicillin from reaction media as well as to evaluate the parameters of antibiotic adsorption onto activated carbon. Experimental Chemicals and ReagentsAmoxicillin was kindly donated by Royton Ltda, Brazil. 6-aminopenicillanic acid (6-APA) and blue dextran were supplied by Winlab and Sigma-Aldrich, respectively. All other reagents were of analytical grade from different commercial brands. AdsorbentActivated ...

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Section: Kinetic Data Of Amoxicillin Adsorption Onmentioning

confidence: 49%

Activated Carbon Adsorbent for the Aqueous Phase Adsorption of Amoxicillin in a Fixed Bed

et al. 2010

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“…This discrepancy might have come from the diffusion coefficient value of BHCl used in the estimation. Although the reported values were similar within an order of magnitude, but they still varied to a certain degree, depending on the measurement conditions (Brounéus et al 2001;Silva et al 2005). On the other hand, strong linearity bewteen release rates from devices with different channel geometry also supports the accuracy of the microfluidic modulation of release rate.…”

Section: Discussionmentioning

confidence: 62%

Controlled release of bupivacaine HCl through microchannels of biodegradable drug delivery device

Lee

Yang

Ryu

2012

Biomed Microdevices

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Local and prolonged delivery of local analgesics is much desired for post-operative pain management. For delivery of local analgesics at a constant rate over couple of days, a microfluidic device comprised of a drug reservoir and microchannels for drug release was developed using a biodegradable polymer, 85/15 poly(lactic-co-glycolic acid). Unlike conventional methods relying on material property, this device enables convenient modulation of the release speed of drugs by a simple change of the channel geometry such as the length and cross-sectional area. Bupivacaine was selected as our model local analgesic drug and its diffusional transport through microchannels was studied using the microfluidic devices. However, since the salt form of bupivacaine, bupivacaine hydrochloride, has pH-dependent solubility, its precipitation in microchannels had an adverse impact on the release performance of the microfluidic drug delivery devices. Thus, in this investigation, the diffusional transport and precipitation of bupivacaine hydrochloride in microfluidic channels were studied using in vitro release experiments and optical analysis. Furthermore, a concept of co-delivery of bupivacaine hydrochloride together with acidic additives was demonstrated to achieve a zero-order delivery of bupivacaine hydrochloride without the clogging of microchannels by its precipitation.

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“…Conforme reportado por diversos autores, 9,34,35 esse comportamento é atribuído ao lento processo de transferência de massa em que a difusão intrapartícula é dominante para essa fase estacionária. Com relação ao cromatograma apresentado na Figura 5S, 14 é possível observar uma melhor resolução, com largura de base relativamente pequena e separação por linha base. Silva Jr. 6 reportou que esse comportamento é devido à alta eficiência da coluna em que a taxa de transferência de massa é alta, sendo os mecanismos convectivos dominantes nesta coluna quiral.…”

Section: Experimentosunclassified

“…Essas incluem as fases baseadas em dialil-L-tartardiamida com ligações cruzadas (Kromasil CHI-DMB e Kromasil CHI-TBB) [14][15][16][17][18][19][20][21][22] e as fases baseadas em ciclodextrinas. 23,24 Embora ainda tenham sido pouco estudadas, as FEQ baseadas em dialil-L-tartardiamida têm apresentado, além de uma boa capacidade de saturação, um elevado número de pratos teóricos quando comparados com outras fases.…”

Section: Introductionunclassified

Separação cromatográfica quiral de anestésicos a partir de soluções diluídas e concentradas em escala preparativa

Silva¹,

Barreto²,

Santana³

2009

Quím. Nova

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Recebido em 3/3/08; aceito em 31/10/08; publicado na web em 2/2/09 CHIRAL CHROMATOGRAPHIC SEPARATION OF ANESTHETICS FROM DILUTE AND CONCENTRATED SOLUTIONS UNDER PREPARATIVE SCALE. In this work the separation of the chiral anesthetic compounds ketamine and bupivacaine was development using two chiral stationary phases (CSP). Ketamine enantiomers were well separate in the polysaccharide-based CSP (microcrystalline cellulose triacetate -MCTA) while bupivacaine in the tartardiamide-based CSP (Kromasil CHI-TBB). In both cases, the effect of temperature was investigated under analytical conditions. An improvement in the separation performance with temperature was observed. Thermodynamic parameters were evaluated by the van't Hoff plot. We concluded that enthalpic effects controlled the retention in these chiral columns. The enantiomers of ketamine and bupivacaine were separated under overloaded conditions with a good performance.Keywords: enantiomer separation; chiral stationary phases; liquid chromatography. introduçãoA separação de isômeros ópticos é importante para o desenvolvimento e a manufatura de numerosos terapêuticos. No intuito de conferir a composição dos fármacos, bem como estudos farmacocinéticos e clínicos mais elaborados, a habilidade para obter quantidades destes isômeros ópticos separadamente tornou-se de essencial importância. Muitos fármacos são administrados como uma mistura racêmica. No organismo, a maioria dos enantiômeros se comporta como duas entidades diferentes; processos controlados pela estereosseletividade, tais como absorção do fármaco, distribuição, metabolismo e eliminação, podem diferir substancialmente entre os enantiômeros. Como exemplo clássico da importância da quiralidade na indústria farmacêutica, podemos citar o caso da talidomida. Na década de 60, a talidomida foi comercializada na sua forma racêmica como um sedativo, para aliviar náuseas matinais em gestantes. Esse medicamento foi retirado do mercado após ter sido constatado apresentar sérios efeitos colaterais. Estudos posteriores confirmaram que apenas o R-enantiômero possui a atividade sedativa desejada, enquanto que o S-enantiômero apresenta propriedades teratogênicas, levando a deformações congênitas em fetos, quando administrado em gestantes.2 Durante a última década, houve grande interesse quanto à obtenção de enantiômeros em sua forma opticamente pura, devido a razões científicas e econômicas, sendo a indústria farmacêutica a principal interessada. 3 Entre 1992 e 2000, o mercado mundial para compostos químicos opticamente puros aumentou de US$ 30 bilhões para uma estimativa de US$ 100 bilhões, com quase duas dúzias de companhias que se especializaram em separações quirais. 5 Rekoske 4 relatou que entre as 500 drogas mais vendidas no mundo, 269 já estavam sendo comercializadas como um único enantiômero.A cromatografia é um processo de separação baseado no equilíbrio de distribuição dos componentes entre duas diferentes fases: a estacionária e a móvel. O transporte seletivo é o resultado da tendência do sistema para evol...

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Chromatographic Separation of Bupivacaine Enantiomers by HPLC: Parameters Estimation of Equilibrium and Mass Transfer Under Linear Conditions

Cited by 19 publications

References 22 publications

Activated Carbon Adsorbent for the Aqueous Phase Adsorption of Amoxicillin in a Fixed Bed

Activated Carbon Adsorbent for the Aqueous Phase Adsorption of Amoxicillin in a Fixed Bed

Controlled release of bupivacaine HCl through microchannels of biodegradable drug delivery device

Separação cromatográfica quiral de anestésicos a partir de soluções diluídas e concentradas em escala preparativa

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