Effect of temperature and chain length of added primary amines on the sphere to rod transition of aqueous ionic micelles

The importance of micelles as templates for nanomaterials is growing day by day. This resulted in an increasing interest for micelles in different sizes and shapes. Addition of n-amines to micellar solutions was found to bring change in the shape of the micelles from sphere to rod in aqueous ionic micellar solutions. The change in shape is qualitatively obtained from sudden change in the slope of pH versus amine concentration plots because the degree or protonation of n-alkylamines depends on the shape of micelles. In the present investigation, pH is measured at different temperatures to elucidate the influence of addition of n-amines on sphere-to-rod transition in aqueous micellar solutions. The surfactants employed in the present investigation are cetyltrimethyl ammonium bromide (CTAB), cetylpyridinium chloride (CPC), and sodium dodecyl sulphate (SDS).As the amine concentration is increased, the pH increases linearly at certain amine concentration and the slope of the resulting straight line changes on further addition of amine. It is noticed that increasing temperature requires more amine for structural transition of aqueous ionic micelles. It is also observed that the effectiveness of added amines leading to shape transition from sphere to rod is in the order of C8NH2>C7NH2> C6NH2.

Poloxamer-enhanced solubility of griseofulvin and its related antifungal activity against Trichophyton spp

Abstract Poorly water-soluble drugs, such as the antifungal drug griseofulvin (GF), exhibit limited bioavailability, despite their high membrane permeability. Several technological approaches have been proposed to enhance the water solubility and bioavailability of GF, including micellar solubilization. Poloxamers are amphiphilic block copolymers that increase drug solubility by forming micelles and supra-micellar structures via molecular self-association. In this regard, the aim of this study was to evaluate the water solubility increment of GF by poloxamer 407 (P407) and its effect on the antifungal activity against three Trichophyton mentagrophytes and two T. rubrum isolates. The GF water solubility profile with P407 revealed a non-linear behavior, well-fitted by the sigmoid model of Morgan-Mercer-Flodin. The polymer promoted an 8-fold increase in GF water solubility. Fourier-transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), and 2D nuclear magnetic resonance (NMR Roesy) spectroscopy suggested a GF-P407 interaction, which occurs in the GF cyclohexene ring. These results were supported by an increase in the water solubility of the GF impurities with the same molecular structure. The MIC values recorded for GF ranged from 0.0028 to 0.0172 mM, except for T. Mentagrophytes TME34. Notably, the micellar solubilization of GF did not increase its antifungal activity, which could be related to the high binding constant between GF and P407.

Chiral separation of four acidic drugs by micellar electrokinetic chromatography with ionic liquid-based surfactant / 中国药科大学学报

@#In this paper, micellar electrokinetic chromatography (MEKC) with glucose-β-cyclodextrin (Glu-β-CD) as chiral selector and ionic liquid surfactant N-butyl-N-methyl pyrrolidine lauryl sulfate ([C4MP] [C12SO4]) micelles formed at low pH as a pseudo stationary phase was applied for the chiral separation of four acidic drugs naproxen,warfarin, ketoprofen and ibuprofen.Under the same conditions,significantly improved separation of tested drug enantiomers was achieved with the MEKC system based on [C4MP][C12SO4] compared with the system based on the conventional surfactant sodium dodecyl sulfate (SDS).Several primary parameters affecting enantioseparation such as type and proportion of organic modifier, concentration and pH of the running buffer, concentration of chiral selector,concentration of ionic liquid surfactant and applied voltage were systematically investigated.

Determination of five saponins in Xuesaitong Dropping Pills by micellar electrokinetic chromatography and evaluation method of between-batch consistency / 中国中药杂志

The present study determined five saponins in Xuesaitong Dropping Pills(XDP) by micellar electrokinetic chromatography(MEKC), and evaluated between-batch consistency by MEKC fingerprints and similarity analysis. A background buffer was composed of 20 mmol·L~(-1) sodium tetraborate-20 mmol·L~(-1) boric acid solution(pH 8.5), 55 mmol·L~(-1) sodium dodecyl sulfate(SDS), 23 mmol·L~(-1) β-cyclodextrin, and 13% isopropyl alcohol. All separations were performed at 25 ℃,20 kV and the detection wavelength was set at 203 nm. The separation channel was a fused silica capillary with a dimension of 75 μm I.D. and a total length of 50.2 cm(effective length of 40.0 cm). The contents of notoginsenoside R_1, and ginsenosides Rg_1, Re, Rb_1, Rd were determined with their quality control ranges set. The fingerprints of XDP were established and the between-batch consistency was evaluated by similarity analysis. The contents of five saponins from the 19 batches of XDP were stable in the fixed ranges. Statistical analysis was carried out on the results of multiple batches of samples, and the specific quality control ranges were recommended as follows: notoginsenoside R_1 21.92-34.16 mg·g~(-1), ginsenosides Rg_1 83.54-131.78 mg·g~(-1), ginsenosides Re 13.58-19.82 mg·g~(-1), ginsenosides Rb_1 89.40-129.90 mg·g~(-1), and ginsenosides Rd 22.34-35.67 mg·g~(-1). Eleven characteristic peaks were identified in the fingerprints. Five peaks, notoginsenoside R_1 and ginsenosides Rg_1, Re, Rb_1, Rd, were identified with reference standards. The similarities of the 19 batches of samples were all above 0.988, indicating good between-batch consistency. This method is green and simple, and can be used for the quantitative determination and quality evaluation of XDP. It can also provide references for the quality control of other Chinese medicinal dripping pills.

Analysis of Related Substances in Biapenam by Micellar Electrokinetic Capillary Chromatography / 中国药学杂志

OBJECTIVE: To establish a method for analysis of related substances in biapenem with micellar electrokinetic capillary chromatography(MEKC). METHODS: In order to improve the separation selectivity, a zwitterionic surfactant, 3-(N, N-dimethylhexadecylammonium)-propanesulfonate(PAPS) was used. The optimal separation conditions were as follows: the total length of the capillary was 48.5 cm (the effective length was 48 cm), the buffer was 90 mmol•L-1 tris(hydroxymethyl)aminomethane (tris)-phosphate buffer containing 17 mmol•L-1 PAPS and 3 mg•mL-1 polyoxyethylene 23 lauryl ether (Brij 35), the applied voltage was 22 kV, and the capillary temperature was controlled at 30℃. Further more, the specificity, linearity, precision, repeatability, stability and durability were studied. The contents of related substances in biapenem commercial samples were analyzed. RESULTS: The MEKC method, which was a comparable analysis method to HPLC, successfully separated the adjacent impurities of biapenem by using the zwitterionic surfactant PAPS. The specific test showed that this method was especially suitable for the detection of biapenem dimers A, B and open-ring compound. CONCLUSION: In this method, MEKC with zwitterionic surfactant is for the first time applied to the analysis of related substances in biapenem (amphoteric drugs). It provides a feasible analysis method with high sensitivity, good specificity and reproducibility for the quality control of biapenem.

Application of micellar electrokinetic capillary chromatography for identification, quantitative detection and unfolding analysis of interleukin-12 / 南方医科大学学报

OBJECTIVE@#To establish a micellar electrokinetic capillary chromatography-based method for identification and quantitative detection of interleukin-12 (IL-12) and analysis of its unfolding process.@*METHODS@#An uncoated fused-silica capillary (inner diameter 50 μm) with a total length of 48.5 cm (40 cm to the detector) was used for the experiment. The factors influencing the separation efficiency of IL-12 were analyzed, and a standard curve of IL-12 concentration was established. The mixture of IL-12 and anti-IL-12 antibody was incubated in a water bath at 38 ℃ for 40 min, and capillary electrophoresis was then performed under the same conditions. The results were compared with those of IL-12 and anti-IL-12 antibody to identify IL-12. IL-12 and dithiothreitol (DTT) were incubated at 60 ℃ in water bath for different lengths of times, and the unfolding process of IL-12 was analyzed based on electrophoresis results of IL-12 in different states.@*RESULTS@#A micellar capillary electrophoresis on-line sweep method was established with 80 mmol/L borate (pH=9.3) containing 30 mmol/L sodium dodecyl sulfate (SDS) as the buffer solution. This system showed a good linear relationship between the peak area and the mass concentration of IL-12 with a linear correlation coefficient of 0.9991 within the linear range of 2 to 120 ng/L. As the incubation time of IL-12 and DTT prolonged, the disulfide bond of IL-12 gradually opened and resulted in distinct changes in the protein peak.@*CONCLUSIONS@#This capillary electrophoresis-based method is simple and sensitive for IL-2 analysis and allows rapid detection of changes in IL-12 content in the setting of tumors and analysis of the possible causes.

Design of novel micellar nano-traditional Chinese medicine formulations based on anti-tumor mechanisms of traditional composition / 第二军医大学学报

Clinically traditional Chinese medicine (TCM) has been proven to possess obvious anti-tumor effects. It is critical to further explore the effective components and the corresponding mechanism of the TCM against target cells, which also has great significance for developing novel nano-TCM formulations for clinical treatment of tumor. This paper systematically reviews the anti-tumor effects of Chinese herbal compound and the anti-tumor mechanism of single herb. We also summarized the progress in the current traditional nano-TCM preparations. Taking the shikonin in Herba Arnebiae as an example, using the nano-material self-assembly technology, we discussed the design of novel nano-macromolecule TCM formulations while considering the mechanism of single herb and the clinical obstacles.

Solubilization and protection of curcumin by mixed surfactants / 药学学报

The solubilization and protection of curcumin (Cur) by mixed surfactants were studied through the determination about the critical micellar concentration (CMC) of the mixed surfactants of Tween 80 and dodecyl trimethyl ammonium bromide (DTAB), molar solubilization ratio (MSR), degradation rate (k) of Cur in pH 13 solution and mixed surfactant solutions prepared at pH 13. The results showed that when Tween 80 was used alone, it exhibited high solubilization ability but poor stability. DTAB was used alone, it showed strong stability but poor solubilization ability. When DTAB was mixed with Tween 80 at different mole fractions, the stability of Cur was enhanced, and the best stability was observed when the mole fraction of DTAB was 0.4, although the solubilization ability was not the best at this mole fraction, but MSR was increased by 1.7 times compared to DTAB used alone. Mixed surfactant not only increased the solubility but also improved the stability of Cur. In addition, mixed surfactant has the advantages of less dosage and low toxicity, which is worth popularizing in application.

Simultaneous Determination of Ephedrine Hydrochloride ，Pseudoephedrine Hydrochloride ，Methamphetamine Hydrochloride and Paeoniflorin in Xiaoqinglong Granule by Micellar Capillary Electrophoresis Method / 中国药房

OBJECTIVE： To establish the method for simultaneous determination of ephedrine hydrochloride， pseudoephedrine hydrochloride， methamphetamine hydrochloride and paeoniflorin in Xiaoqinglong granule. METHODS： Micellar capillary electrophoresis （MCE） method was adopted. The optimum conditions for the separation were as follows as a fused silica capillary column as the separation channel， the buffer solution composed of 10 mmol/L borax-10 mmol/L SDS （95 ∶ 5， pH 10.5）， detection wavelength of 195 nm， separation voltage of 20 kV， capillary column temperature of 15 ℃，the sampling at a pressure for 0.5 psi×5 s. Two batches of Xiaoqinglong granules were collected from 2 manufacturers to determine the contents of ephedrine hydrochloride， pseudoephedrine hydrochloride， methamphetamine hydrochloride and paeoniflorin. The results of content determination were compared with the results determined by HPLC method stated in Chinese Pharmacopeia of 2015 edition. RESULTS： The linear range of ephedrine hydrochloride， pseudoephedrine hydrochloride， methamphetamine hydrochloride and paeoniflorin were 10-160， 10-160， 1-100， 10-500 μg/mL （r＝0.997 9-0.999 8）， respectively. RSDs of precision， reproducibility and stability tests were all ≤2.74％ （n＝5-6）. The average recoveries were 101.55％， 101.62％， 100.15％， 101.85％ （RSD≤3.94％， n＝6）， respectively. The contents of 4 components determined by micellar capillary electrophoresis were in accordance with the results of HPLC method. CONCLUSIONS： The established MCE method is simple， quick and sensitive， and can be used for simultaneous determination of 4 components mentioned above in Xiaoqinglong granule.

Development of Predictive Quantitative Retention-Activity Relationship Models of Quinolones by Mixed Micellar Liquid Chromatography / 中国药学杂志

OBJECTIVE: To obtain the adequate QRAR models of the half-life (t1/2), clearance(CL), volume of distribution (Vd) and area under concentration-time curve (AUC) of quinolones and elucidate the advantages and limitations of using mixed micellar liquid chromatography for describing and estimating the biological parameters. METHODS: The BMCBrij35/SDSQRAR models using mixed micellar system of Brij35/SDS (85:15 ) as a mobile phase under adequate experimental conditions were developed for the biological parameter estimation of quinolones. The correlation between retention factors and biological activities was investigated using second order polynomial models. The predictive and interpretative ability of the chromatographic models was evaluated in terms of cross-validated data (RMSEC, RMSECV and RMSECVi). RESULTS: The BMCBrij35/SDSQRAR models of t1/2, CL, Vd and AUC were statistically significant and both interpolation and extrapolation of parameters were reasonably adequate. CONCLUSION: The mixed micellar liquid chromatography can simulate the resting membrane potential and the conformation of the long hydrophilic polyoxyethylene chains, which may become a simple, economic, and highly reproducible option for establishing QRAR model.

New Carrier Materials for Particles Drug Delivery System of Irinotecan Hydrochloride / 中国药学杂志

OBJECTIVE: To prepare micelle drug delivery system of irinotecan hydrochloride, which could reduce its side effects and improve the therapeutic effects. METHODS: Firstly, the irinotecan hydrochloride was prepared as phospholipid compound to improve the lipophilicity. The synthesized polycaprolactone-polyethylene glycol copolymer was used as carrier material, then the phospholipid complex of irinotecan hydrochloride was wrapped to prepare a polymer micelle drug delivery system. The optimum prescription and preparation process of micelle drug delivery system of irinotecan hydrochloride were screened by the method of single factor combined with orthogonal test. RESULTS: The liposoluble of phospholipid compound of irinotecan hydrochloride was obviously increased compared with active compound. The irinotecan hydrochloride micelle was spherical and its particle size distribution was uniform. The average entrapment efficiency was 61.32%, and the average drug loading was 2.88%. CONCLUSION: Through this method, the particle size of irinotecan hydrochloride is small and the quality is controllable, and it is hopeful to increase the drug concentration at the target site.

Estudo da separação de glicocorticoides e aplicações em formulações farmacêuticas utilizando eletroforese capilar / Study of the separation of glucocorticoids and application in pharmaceutical formulations using capillary electrophoresis

Estudos envolvendo os glicocorticoides merecem destaque devido a serem hormônios responsáveis pela transferência de informações e instruções às células, desta forma regulando o metabolismo, desenvolvimento, crescimento, função imune e também auxiliam no controle das funções tanto reprodutivas quanto tecidual. Estes também são sintetizados e amplamente utilizados com finalidade terapêutica processos alérgicos, tratamento de doenças autoimunes, em transplantes no pré-operatório e/ou pós-operatório-, devido a sua eficiente ação como imunossupressores e anti-inflamatórios. Os dois primeiros capítulos deste trabalho exibem uma revisão da literatura com foco em considerações gerais sobre os glicocorticoides, metodologias empregadas na análise destes hormônios e fundamentos da eletroforese capilar. Na sequência, o quarto capitulo, mostra a otimização da separação de 17 glicocorticoides utilizando cromatografia eletrocinética micelar devido a alto grau hidrofóbico dos analitos. Para tal, a composição do eletrólito consistiu em 20mM de tetraborato de sódio (pH=9.3) e 30 mM de dodecil sulfato de sódio (como surfactante), e a interação soluto-micela e, portanto, retenção do soluto, foi manipulada com a adição (volume/volume) de solventes orgânicos na composição de até 20% acetonitrila (ACN), 20% etanol (EtOH) e 1% tetrahidrofurano (THF), a qual se baseia num modelo de desenho de misturas (totalizando dez diferentes eletrólitos), e através desta abordagem um ótimo de separação foi obtido (13,3% EtOH, 3,3% ACN e 0,17% THF). A melhor condição de separação foi testada qualitativamente numa amostra de urina de um voluntário que faz uso contínuo de prednisona como terapia corticoidal. As misturas de solventes estudadas neste trabalho afetam a solubilidade dos hormônios na fase aquosa e a estrutura micelar também sofre grande impacto,principalmente na camada de solvatação. O quarto capítulo busca racionalizar tais efeitos através da obtenção de descritores, e as informações contidas nos descritores hidrofóbicos e hidrofílicos são sempre relevantes e contribuem nas correlações encontradas. Obteve três grupos de comportamento distinto, onde a capacidade doadora e aceptora de prótons para a realização de ligações de hidrogênios foram as interações consideradas as mais relevantes para o comportamento observado da separação. E o capítulo final, apresenta possibilidades de aproveitamento no controle de qualidade na indústria farmacêutica, métodos baseados na injeção e tensão inversas foram propostos a fim de ganho de tempo de análise (máximo de 5 minutos), estes foram validados seguindo o protocolo preconizado pela ANVISA (Agência Nacional de Vigilância Sanitária) nos parâmetros: precisão, exatidão, seletividade, linearidade, limites de detecção e quantificação e robustez; e aplicados na quantificação de quatro (diferentes formulações comerciais contendo glicocorticoides (prednisona 20 mg, betametasona 4 mg, furoato de mometasona 200 mcg e dipropionato de beclometasona 200 mcg)

Studies involving glucocorticoids deserve to be highlighted because they are hormones responsible for the transfer of information and instructions to cells, thus regulating metabolism, development, growth, immune function and also assist in the control of both reproductive and tissue functions. These are also synthesized and widely used for therapeutic purposes - allergic processes, treatment of autoimmune diseases, in preoperative and/or postoperative transplants - due to their efficient action as immunosuppressants and anti-inflammatories. The first two chapters of this paper present a review of the literature focusing on general considerations about glucocorticoids, methodologies used in the analysis of these hormones and fundamentals of capillary electrophoresis. Subsequently, the fourth chapter shows the optimization of the separation of 17 glucocorticoids using micellar electrokinetic chromatography due to the high hydrophobic degree of the analytes. To this end, the electrolyte composition consisted of 20 mM sodium tetraborate (pH = 9.3) and 30 mM sodium dodecyl sulfate (as a surfactant), and the solute-micelle interaction and therefore solute retention was manipulated with organic solvent in the composition of up to 20% acetonitrile (ACN), 20% ethanol (EtOH) and 1% tetrahydrofuran (THF), which is based on a mixture design model (totaling ten different electrolytes), and through this approach an optimal separation was obtained (13.3% EtOH, 3.3% ACN and 0.17% THF). The best separation condition was qualitatively tested in a urine sample from a volunteer who makes continuous use of prednisone as corticosteroid therapy. The solvent mixtures studied in this work affect the solubility of the hormones in the aqueous phase and the micellar structure also has a great impact, especially on the solvation layer. The fourth chapter seeks to rationalize these effects by obtainingdescriptors, and the information contained in the hydrophobic and hydrophilic descriptors is always relevant and contributes to the correlations found. It obtained three groups of distinct behavior, where the donor and acceptor capacity of protons for the realization of hydrogen bonds were the interactions considered the most relevant for the observed behavior of the separation. And the final chapter presents possibilities of use in quality control in the pharmaceutical industry, methods based on injection and reverse voltage were proposed in order to gain analysis time (maximum of 5 minutes), these were validated following the protocol recommended by ANVISA (Brazilian National Agency of Sanitary Surveillance) in the parameters: precision, accuracy, selectivity, linearity, limits of detection and quantification and robustness; and applied in the quantification of four different commercial formulations containing glucocorticoids (prednisone 20 mg, betamethasone 4 mg, mometasone furoate 200 mcg and beclomethasone dipropionate 200 mcg)

Simultaneous determination of atorvastatin and ezetimibe from combined pharmaceutical products by micellar electrokinetic capillary chromatography

Abstract A rapid and sensitive micellar electrokinetic capillary chromatography method with UV photodiode-array detection was developed for the simultaneous determination of atorvastatin and ezetimibe in fixed dose drug combination. Experimental conditions such as buffer concentration and pH, surfactant concentration, system temperature, applied voltage, injection parameters were optimized in order to improve the efficiency of the separation. The best results were obtained when using fused silica capillary (48 cm length X 50 µm ID) and 25 mM borate buffer electrolyte at pH 9.3 containing 25 mM SDS, + 30 kV applied voltage, 20 ºC system temperature. The separation was achieved in approximately 2 minutes, with a resolution of 7.02, the order of migration being atorvastatin followed by ezetimibe. The analytical performance of the method was verified with regard to linearity, precision, robustness and the limit of detection and quantification were calculated.

Content Determination of Geniposide in Biyuanshu Oral Liquid by Micellar Electrokinetic Capillary Chromatography / 中国中医药信息杂志

Objective To establish a micellar electrokinetic capillary chromatography method for content determination of geniposide in Biyuanshu Oral Liquid. Methods Acetaminophen was used as an internal standard, and the separation was performed on an uncoated fused silica capillary of 52 cm × 50 μm ID (42 cm effective length) with the separation voltage of 25.0 kV. The running buffer contained 50 mmol/L borax, 100 mmol/L sodium dodecyl sulfate and 15％ acetonitrile (pH=10). The sample was injected by pressure (10 s, 0.5 psi) and detected at 238 nm. Results Geniposide was in good linearity range of 15.02–320.48 μg/mL (r=0.9995). The repeatability (low, medium and high concentration of samples) and intermediate precision assays gave satisfactory RSD values of less than 1.77％and 2.01％, respectively. The average recovery of geniposide in Biyuanshu Oral Liquid was 97.50％ and the RSD was 4.43％. The contents of geniposide determined by micellar electrokinetic capillary chromatography were in accordance with the results of HPLC analysis. Conclusion The method is simple, fast, accurate and precise, which can be used for the content determination of geniposide in Biyuanshu Oral Liquid.

Development of alternative methods for the determination of raloxifene hydrochloride in tablet dosage form / O desenvolvimento de métodos alternativos para a determinação do cloridrato de raloxifeno na forma de dosagem em comprimidos

Three methods are proposed for the quantitative determination of raloxifene hydrochloride in pharmaceutical dosage form: ultraviolet method (UV) high performance liquid chromatography (HPLC) and micellar capillary electrophoresis (MEKC). These methods were developed and validated and showed good linearity, precision and accuracy. Also they demonstrated to be specific and robust. The HPLC and MEKC methods were tested in regards to be stability indicating methods and they showed to have this attribute. The UV method used methanol as solvent and optimal wavelength at 284 nm, obeying Lambert-Beer law in these conditions. The chromatographic conditions for the HPLC method included: NST column C18 (250 x 4.6 mm x 5 µm), mobile phase water:acetonitrile:triethylamine (67:33:0,3 v/v), pH 3.5, flow rate 1.0 mL min^-1, injection volume 20.0 µl, UV detection 287 nm and analysis temperature 30 °C. The MEKC method was performed on a fused-silica capillary (40 cm effective length x 50 µm i.d.) using as background electrolyte 35.0 mmol L^-1 borate buffer and 50.0 mmol L^-1 anionic detergent sodium dodecyl sulfate (SDS) at pH 8.8. The capillary temperature was 32°C, applied voltage 25 kV, UV detection at 280 nm and injection was perfomed at 45 mBar for 4 s, hydrodimanic mode. In this MEKC method, potassium diclofenac (200.0 µg mL^-1) was used as internal standard. All these methods were statistically analyzed and demonstrated to be equivalent for quantitative analysis of RLX in tablets and were successfully applied for the determination of the drug...

Três métodos são propostos para a quantificação de cloridrato de raloxifeno em sua forma farmacêutica de comprimidos: espectrofotometria no ultravioleta (UV), cromatografia líquida de alta eficiência (HPLC) e eletroforese capilar micelar (MEKC). Estes métodos desenvolvidos e validados demonstraram linearidade, precisão e exatidão. Também foram específicos e robustos. Os métodos HPLC e MEKC foram desenvolvidos para indicar a estabilidade do fármaco e demonstraram ter este atributo. O método UV usou metanol como solvente e comprimento de onda de 284nm, obedecendo a Lei de Lambert-Beer nestas condições. Os parâmetros cromatográficos para o método HPLC foram: coluna NST C18 (250 x 4,6 mm x 5 µm), fase móvel composta de água:acetonitrila:trietilamina (67:33:0,3 v/v), pH 3,5, vazão da fase móvel de 1,0 mL min^-1, volume de injeção de 20 µl, detecção no comprimento de onda de 287 nm e temperatura de análise de 30°C. O método MEKC foi realizado utilizando capilar de sílica fundida (40 cm de comprimento efetivo x 50 µm de diâmetro interno) usando como fase móvel solução tampão borato 35.0 mmol L^-1 e solução de dodecil sulfato de sódio (SDS) 50.0 mmol L^-1 pH 8,8. A temperatura de análise foi de 32 °C, com voltagem aplicada de 25 kV, detecção no comprimento de onda de 280 nm e injeção da amostra realizada a 45 mBar por 4 s em modo hidrodinâmico. Para este método MEKC, foi utilizado diclofenaco de potássio (200.0 µg mL^-1) como padrão interno. Todos os métodos foram analisados estatisticamente e demostraram ser equivalentes para a análise quantitativa de raloxifeno em comprimidos e foram aplicados com sucesso na determinação do fármaco...

Photostability of nifedipine in monolaurin solid matrix and micellar solution.

The purpose of this study is to evaluate the photostability of nifedipine (NIF) in solid monolaurin (ML)-based matrix and the micellar solutions thereof. NIF loaded-ML matrices at concentrations of 1:1, 1:4 and 1:9 w/w were prepared using a fusion-high shear homogenization method and characterized using differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). The absence of an endothermic melting peak at 173° C in the 1:4 and 1:9 w/w NIF-ML matrices indicates that NIF is in an amorphous state. The 1:1 w/w NIFML matrix showed an endothermic peak at 154° C indicating the transformation of NIF into polymorph III. Stability-indicating HPLC method was developed and validated to quantify NIF and its degradation product. Photoexposed 1:1, 1:4 and 1:9 w/w NIF-ML matrices exhibited 2.1, 4.6 and 17 fold slower first-order degradation rates as compared to the NIF powder. After 24 days of exposure, the percent drug remaining in the 1:9 w/w NIF-ML matrix was 85% as compared to only 5% in pure NIF powder. The micellar solutions exhibited 7-fold slower degradation kinetics than the aqueous solution. The results of this study indicate that the stability of nifedipine can be improved by formulation into monoglycerides matrix.

Rapid Detection of Acetylbritannilactone from Inula britannica in Plasma of Rats by Online Sweeping-Micellar Electrokinetic Chromatography / 中草药·英文版

Objective: To establish a rapid method for detecting acetylbritannilactone (ABL) by online sweeping-micellar electrokinetic chromatography (MEKC) and to elevate the sensitivity of the detection. Methods: The combination of online sweeping technique with MEKC was used to determine the content of ABL in the extract of Inula britannica in plasma of rats. Results: ABL was completely separated within 15 min in running buffer and sample buffer. The optimal conditions were as follows: on uncoated fused quartz silica capillary, with separation voltage of 23 kV, capillary temperature of 25 °C, and detection wavelength of 195 nm. The regression equations revealed good linear relationships between the peak area and concentration of ABL (r = 0.998), with the detection limits of 0.005-0.15 mg/mL. The relative standard deviations of migration time and peak areas for intra- and inter-batch were < 2.45% and < 2.26%, respectively. The recovery rate of this method was 96.3%-97.2%. Conclusion: This method provides some advantages in separation speed, testing sensitivity, and operating convenience, with low sample and reagent consumption. The online sweeping-MEKC is an effective method for pharmacokinetic study and analysis on tracing biological samples. © 2014 Tianjin Press of Chinese Herbal Medicines.

Quantitative bioanalytical and analytical method development of dibenzazepine derivative, carbamazepine: A review☆ / 药物分析学报

Bioanalytical methods are widely used for quantitative estimation of drugs and their metabolites in physiological matrices. These methods could be applied to studies in areas of human clinical pharma-cology and toxicology. The major bioanalytical services are method development, method validation and sample analysis (method application). Various methods such as GC, LC-MS/MS, HPLC, HPTLC, micellar electrokinetic chromatography, and UFLC have been used in laboratories for the qualitative and quan-titative analysis of carbamazepine in biological samples throughout all phases of clinical research and quality control. The article incorporates various reported methods developed to help analysts in choosing crucial parameters for new method development of carbamazepine and its derivatives and also enu-merates metabolites, and impurities reported so far.

Formulation and in vitro/in vivo Evaluation of Zidovudine Contained in Solidified Reverse Micellar Delivery System of Immune Compromised Rats.

Aim of the study was to study the in vitro and in vivo evaluation and correlation of zidovudine (AZT) loaded solidified reverse micellar microparticles (SRMMs). The SRMMs composed of goat fat and Phospholipon® 90H in various ratios (1:1, 2:1, 3:1 and 2:3) were prepared by melt dispersion method. AZT (1 %w/w, 2 %w/w, 3 %w/w and 5 %w/w) were incorporated into the SRMMs and preliminary analysis of the preparations on their stability were done visually. The 1:1 formulation was evaluated for the particle size, percentage yield and in vitro studies which was done using SGF and SIF. The in vivo study was done using Wistar albino rats and the in vitroin vivo correlation (IVIVC) was determined by plotting a graph of the fraction of drug absorbed in vivo versus the fraction of drug released in vitro. The yield of the goat fat extraction was 58 %. The particle size and yield of the solid lipid microparticle (SLM) containing 1 %w/w of AZT were 5.10 ± 0.10m and 86.3 ± 4.70% respectively. The fraction of drugs absorbed in vivo were 0.102 μg, 0.114 μg, 0.115 μg, 0.134 μg and 0.123 μg for 1 h, 3 h, 5 h, 8 h and 12 h respectively. A 1:1 ratio of goat fat and Phospholipon® 90H with a high value of correlation coefficient (r2 = 0.909) suggested good level-A correlation between the in vitro-in vivo data of the SLM obtained in the study.

Application of micellar solubilization technology in pilot production of Chinese materia medica cataplasma containing volatile oil / 中草药

Objective: Through the studies on pilot production of the cataplasma of Chinese materia medica (CMM) containing volatile oil, to provide a rational and feasible preparation technology for the pilot production of CMM cataplasma, so as to promote the development of CMM cataplasma. Methods: The CMM containing volatile oil was extracted by steam distillation method (SDM), ethanol reflux extraction (ERE), and CO2 supercritical fluid extraction (SFE), respectively. The extracts were prepared to cataplasma in order to investigate the effects of extracting methods on the preparation process and quality of CMM cataplasma. The effects of micellar solubilization in the distilled liquid of STM on the quality of cataplasma such as adhesiveness, flexibleness, and stability were also investigated. Results: There was the significant difference among the groups of STM, ERE, and SFE on the quality of cataplasma. The extract by STM was beneficial to the preparation process and enhancement of the quality of cataplasma obviously, while the distilled liquid by STM would cause some limitations such as oil-water separation and volatile oil volatilization losses, which could contribute to obvious difference among batches. These disadvantages by STM would be overcome by the adoption of micellar solubilization technology and the stability would be increased (P < 0.01); segregation happened for the extract by ERE at room temperature, thereby, the water bath heating was needed in the preparation; this characteristics would cause the homogeneous appearance of cataplasma due to some black spots, lower flexibleness of matrix, and the preparation was not easy to control; the extract by SFE contained a lot of impurity of grease and performed half solid. As a result, it was very difficult to blend the extract by SFE with other materials uniformly, the adhesive force of cataplasma was also reduced. In addition, the cost of higher energy consumption and production was another disadvantage for SFE. Conclusion: The STM followed by micellar solubilization would be a feasible preparation technology for the pilot production of CMM cataplasma containing volatile oil, so it is worth popularizing and applying widely.