LC method for the determination of assay and purity of sibutramine hydrochloride and its enantiomers by chiral chromatography

Radhakrishna, T; Narayana, Ch. Lakshmi; Rao, D Sreenivas; Vyas, Kunjbala H.; Reddy, G. Om

doi:10.1016/s0731-7085(99)00303-9

Cited by 29 publications

(15 citation statements)

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“…19,32,33) The concentration of sibutramine in the filtrate was then analyzed by UV at 225 nm. 30) Pharmacokinetics. In Vivo Experiments Male Sprague-Dawley rats weighing 280Ϯ20 g were fasted for 12 h prior to the experiments but allowed free access to water.…”

Section: )mentioning

confidence: 99%

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Enhanced Solubility and Bioavailability of Sibutramine Base by Solid Dispersion System with Aqueous Medium

Jang

Kang

et al. 2010

Biological & Pharmaceutical Bulletin

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Sibutramine [1-(4-chlorophynyl)-N,N-dimethyl-a-(2-methylpropyl)cyclobutane methane amine] is a newer antiobesity drug with a novel mechanism of action.1) It contains a potent inhibitor of the reuptake of noradrenaline (NA), serotonin (5-HT) and may stimulate thermogenesis by its activation of b 3 -adrenoceptors in brown adipose tissue. [2][3][4] In human subjects, sibutramine is rapidly metabolized to an Nmono-desmethyl metabolite (desmethylsibutramine [Metabolite I]) and an N,N-didesmethyl metabolite (didesmethylsibutramine [Metabolite II]). The in vivo effects of sibutramine are predominantly the results of the action of the above 2 metabolites. 4-7)Sibutramine hydrochloride monohydrate is the commercially available formulation of sibutramine with the relatively high solubility of 2.9 mg/ml at pH 5.2 and melting point of 190°C. 4,8) However, sibutramine base with low solubility has not been used in commercial formulation. Various oral formulations of sibutramine such as another salt form such as sibutramine mesylate 9,10) and sibutramine tartrate, 11) solid dispersions with poloxamer [12][13][14] and inclusion complex. 15)One of the well established method for increasing the solubility and bioavailability of poorly water-soluble drugs is solid dispersion.16) Several conventional methods such as melting, solvent evaporation and solvent wetting were reported to prepare solid dispersions. 17,18) However, the solid dispersion prepared by melting method with high temperature might chemically decompose the drugs. 19,20) In the case of solvent evaporation and solvent wetting method, the drug in the solid dispersions changed to amorphous form, resulting that the drug might be unstable. 18) Furthermore, a large amount of hydrophilic carriers against drug in these conventional solid dispersions must be needed to improve the solubility of poorly water-soluble drugs. 21,22) In this study, to improve the bioavailability of poorly water-soluble sibutramine base, various sibutramine baseloaded solid dispersions were prepared with water, hydroxypropylmethyl cellulose (HPMC), poloxamer and citric acid using spray-drying technique. The effect of HPMC, poloxamer and citric acid on the aqueous solubility of sibutramine was then investigated. The physicochemical properties of solid dispersion were investigated using scanning electron microscope (SEM), differential scanning calorimetry (DSC) and X-ray powder diffraction. The dissolution and pharmacokinetics in rats of solid dispersion were evaluated compared to the sibutramine hydrochloride monohydrate-loaded commercial product (Reductil ® ). This commercial product is a conventional capsule which contains 100 mg sibutramine hydrochloride monohydrate and is usually taken multiple times a day. Poloxamer has been employed to enhance the solubility and bioavailability of poorly water-soluble drugs. 19,23) HPMC is frequently used in the preparation of conventional pharmaceutical oral dosage form due to its hydrophilic and soft property. 24,25) To develop a novel sibutramine base-...

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Section: )mentioning

confidence: 99%

“…The residue was reconstituted in 50 ml of the mobile phase by vortex-mixing for 15 s and 5 ml of this solution was injected onto the column. 30) …”

Section: )mentioning

confidence: 99%

Enhanced Solubility and Bioavailability of Sibutramine Base by Solid Dispersion System with Aqueous Medium

Jang

Kang

et al. 2010

Biological & Pharmaceutical Bulletin

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“…A análise dos medicamentos por cromatografia líquida de alta eficiência foi realizada pelo método desenvolvido e validado por Radhakrishna et al, 3 utilizando-se cromatógrafo Varian 920 LC equipado com detector ultravioleta (225 nm) e coluna Hypersil C18 (5 µm, 4,6 x 250 mm). A fase móvel foi constituída de trietanolamina 10% (pH ajustado com ácido orto-fosfórico a 6,0) e acetonitrila na proporção 30/70 (v/v).…”

Section: Análise Dos Medicamentos Por Cromatografia Líquida De Alta Eunclassified

“…sibutramina). 2 A sibutramina, identificada quimicamente como uma mistura racêmica dos enantiômeros do cloridrato de N-(1-(4-cloro-fenilciclobutil)-3-metilbutil)-N-N dimetilamina, 3 é uma amina terciária pertencente à classe dos derivados de cicloalquilaminas (Figura 1), os quais foram inicialmente sintetizados como agentes antidepressivos. Atualmente, o uso deste fármaco corresponde à terapia de primeira escolha para o tratamento de obesidade, 4 agindo como um inibidor da recaptação de aminas e causando o aumento da saciedade.…”

Section: Introductionunclassified

Determinação de sibutramina em formas farmacêuticas através de espectroscopia no infravermelho com refletância difusa e métodos de calibração multivariada

Maluf¹,

Pontarolo²,

Cordeiro³

et al. 2010

Quím. Nova

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Recebido em 11/5/09; aceito em 14/9/09; publicado na web em 24/2/10 DETERMINATION OF SIBUTRAMINE IN PHARMACEUTICAL FORMULATIONS BY DIFFUSE REFLECTANCE INFRARED SPECTROSCOPY AND MULTIVARIATE CALIBRATION METHODS. The goal of this work is the development and validation of an analytical method for fast quantification of sibutramine in pharmaceutical formulations, using diffuse reflectance infrared spectroscopy and partial least square regression. The multivariate model was elaborated from 22 mixtures containing sibutramine and excipients (lactose, microcrystalline cellulose, colloidal silicon dioxide and magnesium stearate) and using fragmented (750-1150/ 1350-1500/ 1850-1950/ 2600-2900 cm -1 ) and smoothing spectral data. Using 10 latent variables, excellent predictive capacity were observed in the calibration (n=20, RMSEC=0.004, R= 0.999) and external validation (n=5, RMSEC= 9.36, R=0.999) phases. In the analysis of synthetic mixtures the precision (SD=3,47%) was compatible with the rules of the Agencia Nacional de Vigilância Sanitária (ANVISA-Brazil). In the analysis of commercial drugs good agreement was observed between spectroscopic and chromatographic methods.Keywords: sibutramine; DRIFTS; multivariate calibration. INTRODUÇÃOO excesso de peso e a obesidade têm se tornado um grave problema de saúde pública, principalmente em razão de pacientes obesos apresentarem maiores riscos de doenças arteriais coronarianas, hipertensão, hiperlipidemia, Diabetes mellitus, acidente vascular cerebral, osteoartrite e doença pulmonar obstrutiva.1 Dentre as várias medidas de tratamento disponíveis destacam-se intervenções farmacológicas, não-farmacológicas ou cirúrgicas, sendo que, em geral, medidas farmacológicas incluem medicamentos inibidores do apetite (ex. anfetaminas), inibidores da reabsorção intestinal de gorduras (ex. orlistat) e estimulantes da saciedade (ex. sibutramina). 2A sibutramina, identificada quimicamente como uma mistura racêmica dos enantiômeros do cloridrato de N-(1-(4-cloro-3 é uma amina terciária pertencente à classe dos derivados de cicloalquilaminas (Figura 1), os quais foram inicialmente sintetizados como agentes antidepressivos. Atualmente, o uso deste fármaco corresponde à terapia de primeira escolha para o tratamento de obesidade, 4 agindo como um inibidor da recaptação de aminas e causando o aumento da saciedade. 5Apesar da sibutramina ser um fármaco aprovado pelas agências reguladoras, inclusive a ANVISA, não foi encontrada uma monografia farmacopeica (nacional ou internacional) que descreva procedimentos orientados ao controle de qualidade de matérias-primas ou suas formas farmacêuticas. Em geral, estudos orientados à identificação e quantificação deste fármaco são fundamentados em métodos cromamétodos cromatográficos, usualmente cromatografia líquida de alta eficiência, 6-8 os quais se caracterizam por serem onerosos e demorados. Deste ponto de vista, o desenvolvimento de metodologias rápidas e de baixo custo apresenta-se bastante relevante.A espectroscopia no infravermelho, principalment...

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“…There have been reports of the chiral separation of sibutramine by high-performance liquid chromatography (HPLC) techniques, using Chiracel OD column, 9 proteinbased chiral stationary phase 10 or Chiralcel AGP-stationary phase column.…”

Section: Introductionmentioning

confidence: 99%

Enantiomeric Separation of Sibutramine by Capillary Zone Electrophoresis

Hancu¹,

Hilochie²,

Vlad³

et al. 2015

Journal of the Brazilian Chemical Society

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The chiral separation of sibutramine enantiomers was resolved succesfully by capillary zone electrophoresis using cyclodextrins (CDs) as chiral selectors. A complex screening of several different native and derivatized, neutral and ionized cyclodextrine derivatives was performed. The effects of buffer type, concentration and pH, cyclodextrin type and concentration, applied voltage, capillary temperature and injection parameters on the chiral resolution were examined. The best results on a very short fused silica capillary of 30 cm × 50 μm were obtained using a 50 mmol L −1 phosphate buffer containing 10 mmol L −1 randomly methylated β-CD at a pH of 4.5, 15 kV of voltage, temperature of 15 °C, injection parameters of 30 mbar s −1 and ultraviolet (UV) detection at 220 nm. The analytical performances of the optimized method were verified in terms of linearity, precision and robustness, and limit of detection and quantification were calculated.

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LC method for the determination of assay and purity of sibutramine hydrochloride and its enantiomers by chiral chromatography

Cited by 29 publications

References 1 publication

Enhanced Solubility and Bioavailability of Sibutramine Base by Solid Dispersion System with Aqueous Medium

Enhanced Solubility and Bioavailability of Sibutramine Base by Solid Dispersion System with Aqueous Medium

Determinação de sibutramina em formas farmacêuticas através de espectroscopia no infravermelho com refletância difusa e métodos de calibração multivariada

Enantiomeric Separation of Sibutramine by Capillary Zone Electrophoresis

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