一种抗偏头痛复方制剂体外溶出度的比较研究

 A novel in vitro dissolution profile was developed for formulated drug in combinational form containing naproxen sodium (NAP) and sumatriptan succinate (SUMA). This study was performed to understand the dissolution of the drug in the physiological temperature and pH. Dissolution testing was performed using USP 29 type II testing apparatus rotating at 50 r/min, in 900 mL deaerated buffer （pH 1.2, 4.5 and 6.8） which was maintained at (37±0.5) ℃. Quantification was performed using a developed and validated high performance liquid chromatographic (HPLC) method. Aceclofenac (ACE) was used as internal standard. SUMA, ACE and NAP were eluted at 4.8, 5.7 and 7.9 min, respectively. As expected for enteric coated immediate release (IR) tablets, the dissolution of NAP and SUMA was rapid and essentially complete within 2 h using phosphate buffer (pH 6.8). The comparison of the dissolution profiles was realized by model independent approach using a difference factor (f1), similarity factor (f2) and dissolution efficiency (DE). Statistical results showed the profiles were similar to the reference and the test products. Hence, this method demonstrated to be adequate for in vitro studies of NAP and SUMA in the combinational dosage form, since there is no official monograph, collaborating to the official codes.     

示波极谱滴定法测定咳快好及其片剂

本文介绍用示波极谱滴定法测定咳快好及其片剂，使用汞膜电极为指示电极，钨电极为参比电极。样品液中加入醋酸钠缓冲液使ｐＨ呈５．４～５．７再加入定量过量的四苯硼钠标准液，使咳快好定量没淀，过滤，过量的四苯硼钠用硫酸亚铊标准液四滴，本法快速，简单、准确。平均回收率９９．５４％，相对标准偏差为０．２２％。     

Separation of urea, uric acid, creatine, and creatinine by micellar electrokinetic capillary chromatography with sodium cholate

The capillary electrophoretic separation of the four nonprotein nitrogenous compounds (NPNs; urea, uric acid, creatine, and creatinine) typically employed in clinical and medical settings for the monitoring of renal function is described. Successful resolution of these compounds is achieved with the use of a bile salt micelle system composed of sodium cholate at phosphate buffer pH 7.4. The elution patterns of four NPNs are obtained within 30 min with a voltage of 30 kV. The effect of varying the applied voltage, temperature, and the mole ratio of phosphate buffer with bile salt surfactant on the migration behavior is also examined.     

Development of extended release coevaporates and coprecipitates of promethazine HCl with acrylic polymers: formulation considerations

The present investigation studied a novel extended release system of promethazine hydrochloride (PHC) with acrylic polymers Eudragit RLPO and Eudragit RS100 in different weight ratios (1 : 1 and 1 : 5) using coevaporation and coprecipitation techniques. Solid dispersions were characterized by Fourier-transformed infrared spectroscopy (FT-IR), Differential scanning calorimetry (DSC), Powder X-ray diffractometry (PXRD), Nuclear magnetic resonance (NMR), Scanning electron microscopy (SEM) as well as solubility and in vitro dissolution studies in 0.1 n HCl (pH 1.2), double distilled water and phosphate buffer (pH 7.4). Adsorption test from drug solution to solid polymers were also performed. Selected solid dispersion system was subjected to direct compression and compressed tablets were evaluated for in vitro dissolution studies. The progressive disappearance of drug peaks in thermotropic profiles of coevaporates were related to increasing amount of polymers while SEM studies suggested homogenous dispersion of drug in polymer. Eudragit RLPO had a greater adsorptive capacity than Eudragit RS100 and thus its coevaporates in 1 : 5 ratio exhibited higher dissolution rate with 91.90% drug release for 12 h. Among different formulations, tablets prepared by Eudragit RLPO coevaporates (1 : 5) displayed extended release of drug for 12 h with 90.87% release followed by zero order kinetics (r(2)=0.9808).     

The role of polymer/drug interactions on the sustained release from poly(dl-lactic acid) tablets

The release profiles of model drugs (propranolol HCl, diclofenac sodium, salicylic acid and sulfasalazine) from low molecular weight poly(d,l-lactic acid) [d,l-PLA] tablets immersed in buffer solutions were investigated in an attempt to explore the mechanism of the related phenomena. It was confirmed that drug release is controlled by diffusion through the polymer matrix and by the erosion of the polymer. The pH of the surrounding medium influences the drug solubility as well as swelling and degradation rate of the polymer and therefore the overall drug release process. Physicochemical interaction between d,l-PLA and drug is an additional factor which influences the degree of matrix swelling and therefore its porosity and diffusion release process. Propranolol HCl shows extended delivery time at both examined pH values (5.4 and 7.4) and especially at pH 7.4 where release was accomplished in 190 days, most probably due to its decreased solubility at higher pH values. The acidic drugs gave shorter delivery times especially at pH 7.4. A slower drug release rate and more extended delivery time at pH 7.4 in comparison with that at pH 5.4 was recorded for tablets loaded with diclofenac sodium and salicylic acid. The opposite effect was observed with samples loaded with propranolol HCl.     

Adsorption from Neutral Solutions of Sodium Alkyl Phosphonates on Zinc and Its Passivation

Russian Journal of Physical Chemistry A - Ellipsometry is used to study the adsorption of the sodium salt of decyl phosphonic acid (SDP) on zinc in a borate buffer solution with pH 7.4. It is found...     

磷酸盐缓冲溶液对邻二氮菲-Fe2+氧化法测定羟基自由基的影响

考察了不同浓度、不同体积的pH=7.4磷酸盐缓冲溶液对邻二氮菲-Fe2+氧化法检测羟基自由基体系的影响.将pH=7.4,浓度分别为0.1,0.15和0.2mol/L的磷酸盐缓冲溶液加入邻二氮菲-Fe2+体系中,随着各自缓冲溶液加入量的增加,其ΔA536不断减小,当加入量超过3mL时,ΔA536基本保持不变.采用抗坏血酸清除含有不同浓度磷酸盐缓冲溶液的邻二氮菲-Fe2+体系,实验结果表明,缓冲溶液浓度和加入量的不同,对于测定体系中清除羟基自由基的作用结果有影响.因此,邻二氮菲-Fe2+氧化法测定羟基自由基需明确体系中磷酸盐缓冲溶液的浓度及用量,在明确的统一体系中,才能进行有效的比较.     

A controlled porosity osmotic pump system with biphasic release of theophylline

A controlled porosity osmotic pump system with biphasic release of theophylline was developed for the nocturnal therapy of asthma. The developed system was composed of a tablet-in-tablet (TNT) core and a controlled porosity coating membrane. Release pattern of the developed system was influenced by amount of pore former (18.2-45.5%, w/w of polymer), weight gain (16-26 mg per tablet) of the coating membrane and osmotic agents used in inner layer of the TNT core. When sodium phosphate and sodium chloride were selected as the osmotic agents in inner and outer layer of the TNT core respectively, target release profile was obtained with coating solution cellulose acetate-polyethylene glycol 400-diethyl phthalate (54.5-36.4-9.1%, w/w) at a weight gain of 16-22 mg per tablet. To examine the mechanism of drug release, release profiles of osmotic agents, micro-environmental osmotic pressure and micro-environmental pH of the formulation during dissolution were studied. Micro-environmental osmotic pressure decreased and micro-environmental pH increased continuously during the whole dissolution process, theophylline release was dominated by the successive dissolution of sodium chloride and sodium phosphate. Theophylline solubility increased as environmental pH exceeded 10.8. At the last stage of the biphasic release, micro-environmental pH in the developed formulation reached 10.9, and theophylline release was promoted by its elevated solubility despite of the decrease of micro-environmental osmotic pressure in the developed formulaiton.     

Large-scale recovery and purification ofl-asparaginase fromErwinia carotovora

A large-scale process was developed to purify gram quantities of a therapeutic enzyme,L-asparaginase, from submerged cultures ofErwinia carotovora. Cells were harvested from 150 L of fermentation broth and washed. A cellular acetone powder was prepared and extracted with pH 9.5 borate buffer. After continuous centrifugation and filtration to remove cell debris, the acetone powder extract was adjusted to pH 7.7 and adsorbed onto a 16-L CM-Sepharose Fast Flow column, with a precolumn packed with Cell Debris Remover. The enzyme was desorbed from the catin-exchange column at pH 9.0 and further purified with an affinity column ofl-asparagine Sepharose CL-4B. After dialysis-concentration to remove buffer salt, the enzyme was depyrogenated, formulated, sterile filled, and lyophilized as a single-dose final product. the final-product evaluation included analysis of the content of protein, sodium chloride, glycine, sodium, glucose hydrate, phosphate, and endotoxin, as well as reconstitution, potency, pH, specific activity, uniformity of fill, and sterility. The product was further subjected to visual examination, sodium dodecyl sulfate polyacrylamide gel electrophoresis, native gel electrophoresis, isoelectric focusing, amino acid analysis,N-terminal sequencing, peptide mapping, and immunological comparison.     

Synthesis of nanosized chitosan-poly(acrylic acid) particles by a dropping method

Deoxyribonucleic acid (DNA) vaccines are being investigated extensively because of their excellent potential over conventional protein ones. A suitable DNA carrier, consisting of uniformly dispersed chitosan-poly(acrylic acid) particles with an average size of 30 nm, was successfully synthesized by a dropping method with a ratio of chitosan solution to poly(acrylic acid) solution of 1:1 and was incubated in a buffer solution with a pH value of 3.0. The particle size increased from 35.76 to 45.90 nm when the pH value of the buffer solution was increased from 3.0 to 7.4. After freeze-drying, the non-incubated mixed solution showed a membranous morphology. A powdered product was formed from the mixed solution as incubated in buffer solution with pH values of 3.0 and 5.3. However, when the mixed solution was incubated in a buffer solution of pH 7.4, a mixture of membrane and powder was obtained.     

Screening of aromatase inhibitors in traditional Chinese medicines by electrophoretically mediated microanalysis in a partially filled capillary

An electrophoretically mediated microanalysis method with partial filling technique was developed for screening aromatase inhibitors in traditional Chinese medicine. The in‐capillary enzymatic reaction was performed in 20 mM sodium phosphate buffer (pH 7.4), and sodium phosphate buffer (20 mM, pH 8.0) was used as a background electrolyte. A long plug of coenzyme reduced β‐nicotinamide adenine dinucleotide 2′‐phosphate hydrate dissolved in the reaction buffer was hydrodynamically injected into a fused silica capillary followed by the injection of reaction buffer, enzyme, and substrate solution. The reaction was initiated with a voltage of 5 kV applied to the capillary for 40 s. The voltage was turned off for 20 min to increase the product amount and again turned on at a constant voltage of 20 kV to separate all the components. Direct detection was performed at 260 nm. The enzyme activity was directly assayed by measuring the peak area of the produced β‐nicotinamide adenine dinucleotide phosphate and the decreased peak area indicated the aromatase inhibition. Using the Lineweaver–Burk equation, the Michaelis–Menten constant was calculated to be 50 ± 4.5 nM. The method was applied to the screening of aromatase inhibitors from 15 natural products. Seven compounds were found to have potent AR inhibitory activity.     

Enhancement of Dissolution Behavior of Aceclofenac by Complexation with β-Cyclodextrin-Choline Dichloride Coprecipitate

The objective of the present investigation was to study the effect of presence of choline dichloride (CDC) in β-cyclodextrin (β-CD) on in vitro dissolution of aceclofenac (AF) from molecular inclusion complexes. The molecular inclusion complexes of AF with β-CD coprecipitated with CDC in 1:1 and 1:2 M ratio were prepared using kneading method. In vitro dissolution of pure drug, physical mixtures, and cyclodextrin inclusion complexes (AF-β-CD-CDC) were carried out. Molecular inclusion complexes of aceclofenac with coprecipitated β-CD showed considerable increase in the dissolution rate in comparison with physical mixture and pure drug in 0.1 N HCl, pH 1.2 and phosphate buffer, pH, 7.4. Inclusion complexes with 1:2 M ratio showed maximum dissolution rate in comparison to other ratios. FTIR spectroscopy and differential scanning calorimetry studies indicated no interaction between AF and β-CD-CDC in complexes in solid state. Dissolution enhancement was attributed to the formation of water soluble inclusion complexes with the precipitated form of β-CD. The in vitro release from all the formulations was best described by first order kinetics (R ² = 0.9354 and 0.9268 in 0.1 N HCl and phosphate buffer, respectively) followed by Higuchi release model (R ² = 0.9029 and 0.9578 in 0.1 N HCl and phosphate buffer, respectively). In conclusion, dissolution of aceclofenac can be enhanced by using the β-CD-CDC coprecipitate as a host molecule.     

Effects of the limited analyte solubility on its mobility and zone shape: electrophoretic behavior of sanguinarine and chelerythrine around pH 7

Electrophoretic mobilities and shapes of zones of sanguinarine and chelerythrine in aqueous media around pH 7 are affected by limited solubility of their uncharged forms and by the pH-dependent chemical equilibrium between cationic and uncharged forms of these alkaloids. The sanguinarine solubility in sodium MOPS of pH 7.4 was estimated at 50 micromol x L(-1). Sanguinarine zones in this buffer have the shape of tailed peak with concentration-independent mobility if the injected sanguinarine concentration exceeds this solubility limit only slightly. The chelerythrine solubility is higher because of lower dissociation constants of its cations. Precipitation of sanguinarine and chelerythrine with the phosphate anions decelerates their electrophoretic transport in phosphate buffer. Sanguinarine solubility is 5 micromol x L(-1) at the most in 13 mmol x L(-1) sodium phosphate buffer of pH 7.4. Acidifying of the sample up to pH 3 decreases the tailing of the peaks of sanguinarine and chelerythrine and contributes to the rise of sharp maxima of their migrating zones. Any capillary coating deteriorates the peak shape.     

紫外可见分光光度法快速测定苯硫酚

设计合成一种全新的苯硫酚检测探针。以试卤灵钠为主要原料,在三乙胺催化下与2,4-二硝基氯苯合成了7-(2’,4’-二硝基苯氧基)-3H-吩噁嗪-3-酮,产率为41.7%。在p H 7.4的磷酸盐缓冲溶液中,该化合物能与苯硫酚发生亲核取代反应,反应体系在可见光区λ=580 nm处有强吸收。该探针测定苯硫酚的线性范围为0.1~20μmol/L,检出限为8.9×10–8 mol/L,精密度为3.7%(n=8),回收率为106%。该方法可快速检测环境及生物体中的苯硫酚。     

PEC films prepared from Chitosan-Alginate coacervates

Chitosan-alginate polyelectrolyte complex (PEC) have been prepared in situ in beads and microspheres. This study examines the preparation of suitable chitosan-alginate coacervates for casting into homogeneous PEC films for potential applications in packaging, controlled release systems and wound dressings. Coacervation between chitosan and alginate was rapid, but the rate may be controlled with the addition of water miscible organic solvents. Compared with ethanol and PEG200, acetone was the more promising solvent moderator. Suspensions of fine, uniformly dispersed coacervates were produced by a dropwise addition of 0.25% w/v chitosan solution (solvent: 1: 1 v/v of 2% acetic acid and acetone) into 0.25% w/v sodium alginate solution in water under rapid agitation. The PEC films were transparent and flexible. They exhibited high permeability to water vapor, but resisted complete dissolution in 0.1 M HCI, distilled water and pH 7.4 phosphate buffer solution. Microscopic heterogeneity in the films could be reduced by immersion in aqueous media, but this was accompanied by modifications in the thickness, permeability and mechanical property of the films.     

Dissolution of copper nanopowders in inorganic biological media

Electroexplosive copper nanopowders with dispersion 3.2, 5.0, 6.8, and 12.0 m² g⁻¹ were dissolved in distilled water, physiological (saline) solution, and phosphate buffer. From experimentally determined concentrations of dissolved copper and pH of the solution kinetic curves were constructed and kinetic and thermodynamic analysis was performed of the possible chemical reactions. The influence of the powder dispersion and the nature of solvents on the kinetic parameters of dissolution were considered.     

Permselectivity of neurotransmitters at overoxidized polypyrrole-film-coated glassy carbon electrodes

The permselectivity of neurotransmitters such as dopamine, epinephrine, and norepinephrine at overoxidized polypyrrole (OPPY)-film-coated glassy carbon electrodes has been investigated. The chemically-modified electrodes exhibit attractive permselectivity and antifouling properties of rejecting anionic species, e.g. ascorbate, etc. Compared with the response of neurotransmitters at modified electrodes overoxidized in phosphate buffer solution (pH 7.4), higher sensitivity and reversibility response can be obtained at modified electrodes overoxidized in sodium hydroxide solution. The effect of film thickness on the permselective response was tested. Rotating disk electrode experiments were used to determine the apparent diffusion coefficients of several electroactive solutes in the OPPY films. The influence of the hydrophobicity of the organic ions on the permeability within the polymer films was discussed. Dopamine and epinephrine were determined at the 1 x 10(-6)-1 x 10(-4) M level by means of voltammetry after an exposure period of 2 min in 0.1 M phosphate buffer (pH 7.4) with detection limits of 8 x 10(-7) M and 6 x 10(-7) M respectively.     

多氢键反应-纳米金共振散射光谱法测定三聚氰胺

在pH 7.0的磷酸盐缓冲溶液中,氯金酸被3,5-二羟基苯甲酸(DBA)还原生成的金纳米粒子在610nm处产生一个较强的共振散射峰;当有三聚氰胺(MA)存在时,DBA与MA形成多氢键化合物而不能还原氯金酸,导致610 nm处共振散射峰的强度降低.三聚氰胺的浓度在5.0×10 -6～4.0×10-5 mol·L-1范围内...     

Characterization of factors affecting the release of low-solubility drug from prolonged release tablets

Diclofenac sodium (2-[(2,6-dichlorophenyl)amino]benzeneacetic acid monosodium salt) was investigated as a low-solubility drug and Naklofen^® retard prolonged release tablets, containing 100 mg of diclofenac sodium as a prolonged release lipophilic matrix system using factorial design approach. First, the solubility characteristics of diclofenac sodium in aqueous media with various ionic strengths, ionic compositions and pH in the range of 1-8 were determined. The obtained results showed that the solubility of diclofenac sodium depends mainly on pH of the aqueous medium and less on the composition and ionic strength of the medium. Next, the estimation of the effects of six different factors (type of the dissolution apparatus, rotation speeds of the stirring elements, pH, ionic strengths of dissolution medium, the applied salt, and the producer of the on-line connected dissolution apparatus and UV spectrophotometer) on the release of diclofenac sodium, using the two-level six-factorial design was investigated. It was found that rotation speeds of the stirring elements, pH, and ionic strengths of the dissolution medium have a significant impact on the drug release and should be further followed in future drug release analyses. The advantages of the factorial design approach are obvious in this work. It is a very economic way of obtaining the maximum amount of information in a short period of time, especially in the case of prolonged release formulations where each experiment requires at least 24 h.     

In Vitro–In Vivo Correlation of Tianeptine Sodium Sustained-Release Dual-Layer Tablets

Tianeptine tablets are currently marketed to be designed for immediate-release tablets. The tianeptine has a short half-life, making it difficult to design for sustained-release tablets and achieve bioequivalence with the tianeptine immediate-release tablet (Stablon^®). We established the in vitro–in vivo correlation (IVIVC) of three formulations of tianeptine sustained-release tablets according to their granule size. To evaluate sustained drug release, in vitro tests were performed in pH 1.2 media for 24 h. In vivo pharmacokinetic analysis was performed following oral administration of reference drug and test drug to beagle dogs. The dissolution profile revealed delayed release as the size of the granules increased. The dissolution results were confirmed in pharmacokinetic analysis, showing that the half-life was delayed as granule size increased. The final formulation and reference drug showed an equivalent area under the curve (AUC). Through this, IVIVC was established according to the size of the tianeptine sodium granules, which is the purpose of this study, and was used to predict in vivo pharmacokinetics from the formulation composition. This approach may be useful for determining optimal formulation compositions to achieve the desired pharmacokinetics when developing new formulations.