高效液相色谱同时测定四种精神药物和抗癫痫药物

建立一种高效液相法同时测定血液中苯巴比妥、安定、苯妥英和卡马西平的药物浓度的方法．     

Improvement of bioavailability of water insoluble drugs: Estimation of intrinsic bioavailability (Short Communication)

A series of attempts to enhance the bioavailability of water insoluble drugs have been made by the fine grinding technique using a planetary ball mill in wet milling process. Here, the possibility of improving the dissolution properties of water insoluble drugs such as ursodeoxycholic acid (UDCA), diphenyl hydrantoin (phenytoin) and biphenyl dimethyl dicarboxylate (DDB) based on ultra-fine grinding process has been discussed with comparison to experimental data. Also examined was the intrinsic bioavailability estimated based on a molecular modeling approach and thermophysical data.     

Aqueous solubility of poorly water-soluble drugs: Prediction using similarity and quantitative structure-property relationship models

The aqueous solubility of poorly water-soluble drugs is an important property of many factors affecting their bioavailability such as the solubility and rate of dissolution in water. The quantitative structure-property relationship approach using genetic algorithm was applied to make models for predicting some poorly water-soluble drugs such as ursodeoxycholic acid, diphenyl hydrantoin and biphenyl dimethyl dicarboxylate. The experimental solubility data of 3518 chemical structures were collected from the web and used to build a model. Three data sets of 50 compounds were extracted according to their structural similarity with each drug. A fast and predictive similarity based approach was developed and validated with conventional method. This can be used to predict the aqueous solubility for drugs by using a small set of compounds, especially for poorly water-soluble compounds. Moreover, the estimation values of various sets were further compared with fine grinding experiment data.     

紫外光解水中苯妥英钠的效能及机理研究

研究了紫外(UV)在不同条件下光解苯妥英钠(DPH)的效能.结果 表明,在DPH浓度为20 μmol/L,pH为7.0,反应温度为25℃,辐射光强为0.31 μE/s的条件下,DPH在UV辐照90 min后的去除率可达85.4％,在该条件下DPH的量子产率为0.664 mol/E.溶液pH及腐殖酸(HA)对UV体系下D...     

Controlled release of phenytoin for epilepsy treatment from titania and silica based materials

Template technique was used to obtain well ordered nanostructured materials: mesoporous silica and nanostructured titania tubes. This technique permits the synthesis of solids with controlled mesoporosity, where a large variety of molecules that have therapeutic activity can be hosted and further released to specific sites. In this work phenytoin (PH), a drug used in epilepsy treatment, was loaded in ordered mesoporous silica (SBA 15) and nanostructured titania tubes (TiO₂). The pure materials and those containing PH were characterized by X-ray diffraction, FTIR spectroscopy, transmission electron microscopy (TEM), scanning electron microscopy (SEM) and N₂ adsorption–desorption at 77 K. In order to determine the loading capacity of the antiepileptic drug on these silica- and titania-based materials, the loading and release of PH was investigated using UV–vis spectroscopy. Tubular structures were found for the titania samples, for which the X-ray diffractograms showed to be formed by anatase and rutile phases. On the other hand, an amorphous phase was found in the silica sample. A highly ordered hexagonal structure of 1D cylindrical channels was also observed for this material. Loaded PH showed a good stability inside the used materials as observed by spectroscopy analysis. The adsorption and desorption of PH are faster in nanostructured TiO₂ tubes than in mesoporous silica matrix.     

One step liquid phase heterogeneous synthesis of phenytoin over MgAl calcined hydrotalcites

Heterogeneous liquid phase synthesis of phenytoin (5,5-diphenylhydantoin) was carried out over MgAl calcined hydrotalcites for the first time under environmental friendly conditions. The catalytic activity results showed very high conversion (80–95%) and selectivity (90–95%) of the desired product phenytoin over MgAl calcined hydrotalcites. The calcined hydrotalcites can be recycled without further loss in the activity and the possible mechanism of the reaction is also proposed.     

Topical phenytoin nanostructured lipid carriers: design and development

Phenytoin (PHT) is an antiepileptic drug that was reported to exhibit high wound healing activity. Nevertheless, its limited solubility, bioavailability, and inefficient distribution during topical administration limit its use. Therefore, this study aims to develop, characterize nanostructured lipid carriers (NLCs), and evaluate their potential in topical delivery of PHT to improve the drug entrapment efficiency and sustained release. The NLCs were prepared by hot homogenization followed by ultra sonication method using 2³ factorial design. NLC formulations were characterized regarding their particle size (PS), zeta potential (ZP), entrapment efficiency percent (%EE), surface morphology, physicochemical stability, and in vitro release studies. The optimized NLC (F7) was further incorporated in 1%w/v carbopol gel and then characterized for appearance, pH, viscosity, stability, and in vitro drug release. The prepared NLCs were spherical in shape and possessed an average PS of 121.4–258.2?nm, ZP of (?15.4)–(–32.2)?mV, and 55.24–88.80 %EE. Solid-state characterization revealed that the drug is dispersed in an amorphous state with hydrogen bond interaction between the drug and the NLC components. NLC formulations were found to be stable at 25?°C for six months. The stored F7-hydrogel showed insignificant changes in viscosity and drug content (p>.05) up to six?months at 25?°C that pave a way for industrial fabrication of efficient PHT products. In vitro release studies showed a sustained release from NLC up to 48?h at pH 7.4 following non-Fickian Higuchi kinetics model. These promising findings encourage the potential use of phenytoin loaded lipid nanoparticles for future topical application.     

Phenytoin overdose treated with hemodialysis using a high cut‐off dialyzer

We describe the case of a 52‐year‐old man who presented after having ingested an unknown quantity of phenytoin. Peak phenytoin concentration was 51.2 mg/L (therapeutic range 10–20 mg/L). Five days after admission, the patient became comatose and was intubated. Because of persistent toxic phenytoin levels and unchanged clinical status for 12 days, hemodialysis (HD) was prescribed to enhance elimination of phenytoin. HD was performed using a Gambro Theralite^TM filter (Baxter International Inc., Deerfield, USA), a high cut‐off filter that allows the removal of molecules of up to 45 kDa. Phenytoin concentration readily decreased during the 8‐hour HD treatment from 38.9 mg/L to 27.8 mg/L (28.5% decrease); during HD, phenytoin half‐life was 18.5h (compared to 1109.8h before HD and 56.3h after HD), phentyoin clearance averaged 80.1 mL/min and a total of 1.1 g of phenytoin was removed. Albumin removal from the Theralite filter was most important at the beginning of HD. The high clearance of phenytoin obtained with this filter was likely due to its high surface area rather than its capacity to remove the albumin‐phenytoin complex.     

Semisolid matrix filled capsules: an approach to improve dissolution stability of phenytoin sodium formulation

Seven semisolid fill bases were selected for the formulation of 24 capsule formulations, each containing 100 mg of phenytoin sodium. The fill materials were selected based on the water absorption capacity of their mixtures with phenytoin sodium. The fill matrices included lipophilic bases (castor oil, soya oil, and Gelucire (G) 33/01), amphiphilic bases (G 44/14 and Suppocire BP), and water-soluble bases (PEG 4000 and PEG 6000). The drug:base ratio was 1:2. Excipients such as lecithin, docusate sodium, and poloxamer 188 were added to some formulations. The dissolution rate study indicated that formulations containing lipophilic and amphiphilic bases showed the best release profiles. These are F4 (castor oil-1% docusate sodium); F10 (castor oil-3% poloxamer 188); F14 (G33/01-10% lecithin); F17 (G33/01-1% docusate sodium), and F20 (Suppocire BP). Further, the dissolution stability of the five formulations above was assessed by an accelerated stability study at 30°C and 75% RH using standard Epanutin capsules for comparison. The study included the test and standard capsules either packed in the container of marketed Epanutin capsules (packed) or removed from their outer pack (unpacked). Release data indicated superior release rates of castor oil based formulations (F4 and F10) relative to standard capsules in both the unpacked and packed forms. For instance, the extent of drug release at 30 min after 1 month was 91% for F4 and F10 and 20% for standard capsules. Drug release from packed capsules after 6 months storage was 88% for both formulations F4 and F10 and 35% for standard capsules. In conclusion, the pharmaceutical quality of phenytoin sodium capsules can be improved by using a semisolid lipophilic matrix filled in hard gelatin capsules.