Eudragit E as excipient for production of granules and tablets from phyllanthus niruri L spray-dried extract

The aim of this study was to investigate the feasibility of using Eudragit E as a granulating agent for a spray-dried extract fromPhyllanthus niruri to obtain tablets containing a high dose of this product. The granules were developed by wet granulation and contained 2.5%, 5.0%, and 10.0% Eudragit E in the final product concentration. The tablets were produced on a single-punch tablet press by direct compression of granules using 0.5% magnesium stearate as a lubricant. The tablets were elaborated following a 2×3 factorial design, where Eudragit E concentration and compression force were the in-dependent variables, and tensile strength and the extract release of the tablets were the dependent variables. All granules showed better technological properties than the spray-dried extract, including less moisture sorption. The characteristics of the granules were directly dependent on the proportion of Eudragit E in the formulation. In general, all tablets showed high mechanical resistance with less than 1% friability, less moisture sorption, and a slower extract release profile. The Eudragit E concentration and compression force of the tablets significantly influenced both dependent variables studied. In conclusion, Eudragit E was efficient as a granulating agent for the spray-dried extract, but additional studies are needed to further optimize the formuations in order to achieve less water sorption and improve the release of the extract from the tablets. Published: April 27, 2007     

Optimization of the operating conditions of a lab scale Aljet mill using lactose and sucrose: A technical note

Conclusion  The results of the experiments have revealed that the optimal operating conditions for a lab scale Aljet mill are at the high level (110 psi) of the pushing nozzle and the low level (65 psi) of both grinding nozzles, or vice versa. Operating the Aljet mill at high pushing and grinding pressures also produces small particle size; however, the high pressures require more gaseous fluid making the process less efficient. At a very low pushing nozzle pressure as compared with the grinding nozzle pressure, the material kicks back from the mill, reducing the yield. Optimization of the lab scale Aljet mill operating conditions will be very useful in particle size reduction of poorly water-soluble compounds and is particularly beneficial at early stages of drug development when the drug quantity is very limited.     

中心复合实验设计法优化重组毕赤酵母表达猪胰岛素前体的培养基和诱导pH

毕赤酵母中猪胰岛素前体(Porcine Insulin Precursor,PIP)的表达受到培养基组成及培养环境的影响。本文首先通过部分因子法设计实验,筛选出影响PIP表达的显著因子。实验结果表明,在试验范围内,甲醇补料量和硫酸铵浓度为正效应因子,诱导pH为负效应因子。在此基础上,经过快速登高法逼近显著因子的最优值后,再在此值附近利用中心复合法设计实验,最终得到了PIP表达的最佳条件。经过多批次实验验证,在此条件下PIP的表达量为120.4mg/L,比优化前的值41.5mg/L提高了将近两倍。     

新筛选L-精氨酸产生菌发酵培养基的响应面优化

目的:优化谷氨酸棒杆菌YHR-09的发酵培养基以提高L-精氨酸的产量.方法:在研究葡萄糖、硫酸铵、玉米浆和生物素4个单因素实验的基础上,用Design Expert软件的Central Composite Design建立响应曲面模型.结果:YHR-09最佳产酸条件 为:葡萄糖112.95g/L,玉米浆22.61g/L,硫酸铵49.44g/L.在此条件下L-精氨酸的产量为29.36g/L,与预测值(29.57g/L)吻合度较高.结论:通过发酵对比实验可见,菌体浓度的明显提高是L-精氨酸产量上升的重要因素.     

Remediation of a Diesel-Contaminated Soil Using a Fenton-Like Advanced Oxidation Process: Optimization by Response Surface Methodology

Magnetite, a naturally occurring mineral of iron oxide, and zero-valent iron (ZVI) were used to catalyze hydrogen peroxide and initiate a dark Fenton-like reaction of diesel-contaminated loamy sand in a batch system at circumneutral pH. The effects of hydrogen peroxide concentration and catalyst content on the removal efficiency of total petroleum hydrocarbons (TPHs) were studied. A central composite rotatable design was applied and the derived equation for magnetite and ZVI were linear and quadratic, respectively. In both equations, the factor of hydrogen peroxide concentration was more significant than catalyst content. At optimum conditions (4.27 wt% of catalyst content and 2.17 mol/L of hydrogen peroxide), 57% and 67% of TPH removal were achieved by magnetite and ZVI, respectively. The obtained results suggest the potential of ZVI and magnetite to catalyze a heterogeneous Fenton-like reaction at circumneutral pH. It seems that using ZVI, rather than magnetite, as a catalyst may result in slightly more TPH mineralization; however, since magnetite is a naturally occurring mineral, it may be able to compete economically with ZVI.     

Statistical evaluation of influence of viscosity and content of polymer on dipyridamole release from floating matrix tablets: A technical note

Conclusion  The present investigation described the influence of viscosity and content of HPMC on dipyridamole release using 3² full factorial design. All formulations had desired floating lag time (<2 minutes) regardless of viscosity and content of polymeric matrices. Results of multiple regression analysis indicate that both factors significantly affect the diffusion exponent (n), release rate constant (k), and percentage drug release at 1 hour, 4 hours, 6 hours, and 12 hour, (P<.05). Mechanism of drug release was found to be anomalous type to case-II transport depending upon the viscosity and content of polymer. It was found that content of HPMC had a dominant role in the initial phase of drug release, while in the later phase viscosity of HPMC Predominated. Published: August 24, 2007     

Optimization of Protease Extraction from Horse Mango (Mangifera foetida Lour) Kernels by a Response Surface Methodology

The thermophilic protease aqualysin I (AQI) gene (aqul), derived from Thermus aquaticus YT-I, was inserted under the control of the bacteriophage T7 promoter in an expression plasmid. The plasmid was introduced into two strains of E. coli JMI09 (DE3), one carrying and one lacking an F’ episome, which carries the lacI_q gene. Upon cultivation the strain carrying an F’ episome produced AQI as an insoluble fusion protein (74 kDa) with the T7 gene 10 protein. This insoluble protein could not be processed into mature AQI by heat treatment and thus it had no proteolytic activity. On the other hand, when the strain lacking an F’ episome was used as a host cell for aqul expression, non-induced, or leaky, expression occurred, and AQI was produced in a soluble form. This soluble protein could be processed into active AQI by heat treatment. Moreover, when a low concentration of IPTG (0.0125 mM) was added, the amount of active AQI was 2.7 times greater than that produced in a batch culture without induction.     

响应曲面法优化灵芝廉价型深层发酵培养基的研究

为了获得生产用廉价型灵芝发酵培养基,采用中心组合旋转设计法和响应曲面法对低成本培养基组分进行了优化。优化的四个组分为玉米粉(x1)、麸皮粉(x2)、豆饼粉(x3)和蔗糖(x4)。结果表明,灵芝菌体发酵和多糖发酵的培养基预测模型分别为:Y1=15.1–0.31x1–0.34x2+0.36x3–0.44x4–1.26x12–1.98x22–0.85x32–1.15x42–0.59x2x3和Y2=2.0–0.08x1–0.08x2+0.04x3–0.09x4–1.13x12–0.33x22–0.08x32–0.16x42–0.16x2x3–0.10x1x4。从中获得菌体发酵的最优配方为:玉米粉19.7g/L,麸皮粉11.3g/L,豆饼粉6.3g/L,蔗糖19.5g/L;多糖发酵的最优配方为:玉米粉19.6g/L,麸皮粉11.0g/L,豆饼粉6.7g/L,蔗糖19.1g/L。150L发酵罐中试放大结果表明,灵芝菌体的产量为16.92g/L,多糖产量为1.86g/L。所得培养基为灵芝产品的高效低成本生产提供了基础。     

红酵母产类胡萝卜素提取工艺的优化研究

目的:从提取溶剂及提取条件等方面对红酵母产类胡萝卜素提取工艺进行了优化研究。方法:用单因子实验对提取溶剂进行了筛选;用析因试验对提取条件进行了分析研究;通过最陡爬坡实验和中心组合设计实验,优化得到了最佳的类胡萝卜素提取条件。结果:结果表明丙酮和二甲亚砜组成的复合体系是理想的提取溶剂。溶剂添加量、提取温度、提取时间、丙酮与二甲亚砜组分比例都对红酵母产类胡萝卜素提取产生一定影响,其中溶剂添加量和丙酮与二甲亚砜组成比例的影响最为显著(P<0.001)。最佳优化提取条件为:溶剂添加量为42.66%(V/V),丙酮与二甲亚砜组成比例为62.47%(V/V),温度为20℃,提取时间为90min,在此条件下红酵母产类胡萝卜素的最大提取量为5.51μg/ml。结论:实验得到了红酵母发酵产类胡萝卜素溶剂提取条件的一个非常合适的模型。     

Viscoelastic properties of a virucidal cream containing the monoglyceride monocaprin: Effects of formulation variables: A technical note

The viscoelastic properties of the cream formulations were tested by 2 methods (ie, increased stress and increased frequency tests). The rheology experiments indicate that the formulations are stable; they show resistance to external forces, as their elastic properties are sustained whether or not the magnitude or frequency of external forces are increased. The results show that rheological properties of the formulations are affected by the proportion of the oil phase and the amount of carbomer in the aqueous phase, but the effect of monocaprin is modest. Increasing carbomer amount increases viscosity and elasticity. Increasing the oil volume fraction increased the structural stability of the creams. The formulation containing monocaprin, which yielded the most viscoelastic structure was a cream containing 10% oil phase and 0.5% carbomer (Formulation 9).     

Optimization of galacto-oligosaccharide production by Bifidobacterium infantis RW-8120 using response surface methodology

Oligosaccharide (OS) production, cell concentration (2×10⁹ colony-forming unit/ml), lactose concentration (25% wt/vol), reaction time (6 h), and temperature (50°C) were chosen as the central condition of the central composite design (CCD) for optimizing the production process using Bifidobacterium infantis RW-8120 in skim milk. Statistical analysis (P<0.01) revealed that the most relevant variable concerning OS production and yield was the lactose concentration. The coefficient of determination (R ²) is good for the second-order OS production model (0.92) and fairly good for the second-order nonlinear OS yield model (0.816). An increase of lactose concentration and temperature resulted in a higher OS production. The optimal values for OS production appear to be near the area associated with the central points of the modeling design except for the lactose concentration, which was 40% (wt/vol) of the final volume. Received 29 March 2002/ Accepted in revised form 09 August 2002     

Enzymatic synthesis of betulinic acid ester as an anticancer agent: Optimization study

Abstract

Immobilized Candida antarctica lipase, Novozym 435, was used to catalyze the esterification reaction between betulinic acid and phthalic anhydride to synthesize 3-O-phthalyl betulinic acid in n-hexane/chloroform. Response surface methodology based on a five-level, four-variable central composite rotatable design was employed to evaluate the effects of synthesis parameters such as reaction time, reaction temperature, enzyme amount and substrate molar ratio on the yield of ester. Based on the response surface model, the optimal enzymatic synthesis conditions were predicted to be: reaction time 20.3 h, reaction temperature 53.9°C, enzyme amount 145.6 mg, betulinic acid to phthalic anhydride molar ratio 1:1.11. The predicted yield was 65.8% and the actual yield was 64.7%.     

Gastroretentive drug delivery system of carbamazepine: Formulation optimization using simplex lattice design: A technical note

Summary and Conclusion  An attempt was made to develop a gastroretentive drug delivery system of carbamazepine using HPMC, sodium bicarbonate, and EC as matrixing agent, gas-generating agent, and floating enhancer, respectively. A simplex lattice design was applied to investigate the combined effect of 3 formulation variables (ie, amount of HPMC (X ₁), EC (X ₂), and sodium bicarbonate (X ₃). Results of multiple regression analysis indicated that low levels ofX ₁ andX ₂ and a high level ofX ₃ should be used to manufacture the tablet formulation with desired in vitro floating time and dissolution. Formulation S3 was selected as a promising formulation and was found stable at 40°C temperature and 75% RH for 3 months. Published: February 9, 2007     

裂褶菌F17锰过氧化物酶酶活力影响因素的响应面优化(英文)

锰过氧化物酶是真菌分泌的一种糖基化的含有血红素辅基的胞外蛋白,在染料降解和脱色过程中起着重要作用。本实验利用本实验室保存的的白腐真菌裂褶菌Schizophyllum sp.F17产锰过氧化物酶(MnP),研究MnP的酶学性质,并对酶活条件进行优化。实验通过超滤浓缩、DEAE-纤维素、DE52离子交换层析和Sephadex G-75凝胶过滤等步骤,分离纯化得到电泳纯的锰过氧化物酶。该酶蛋白含量为23μg/mL,分子量大小为49.2kDa,在0.1mmol/L H2O2中半衰期为5~6min。Mn2+、H2O2以及酶的用量可以影响MnP酶促反应的效率,在单因子分析法的基础上,通过全因子中心组合设计响应面分析表明:H2O2以及H2O2与酶用量之间的交互作用对酶促反应的作用是最显著的。在优化条件下,酶对偶氮染料金橙G、刚果红显示出较强的脱色能力。     

Optimization of a culture medium for xylanase production by Bacillus sp. using statistical experimental designs

The concentrations of oat spelt xylan, casein hydrolysate and NH4Cl in the culture medium for production of xylanase from Bacillus sp. I-1018 were optimized by means of response surface methods. The path of steepest ascent was used to approach the optimal region of the medium composition. The optimum composition of the nutrient medium was then easily determined by using a central composite design and was found to be 3.16g/l of xylan, 1.94g/l casein hydrolysate, 0.8g/l of NH4Cl. The xylanase production was increased by 135% when the strain was grown in the optimized medium compared to initial medium.     

Optimization of a medium for enhancing nicotine biodegradation by Ochrobactrum intermedium DN2

AIMS: To optimize a medium for nicotine degradation by Ochrobactrum intermedium DN2 in presence of yeast extract, glucose and Tween 80 using response surface methodology (RSM). METHODS AND RESULTS: In this study, the effects of yeast extract, glucose and Tween 80 on nicotine degradation were investigated in flasks using a novel nicotine-degrading bacterium, O. intermedium DN2. A full factorial central composite design was applied in the design of experiments and in the analysis of the experimental data. The results showed that the most significant variable influencing nicotine degradation was yeast extract, followed by glucose, and then Tween 80. Moreover these three factors interacted with each other and combined to produce positive effects on nicotine degradation. The experimental data also allowed the development of an empirical model (P < 0.0001) describing the inter-relationship between independent and dependent variables. By solving the regression equation, the optimal values of the variables were determined as: yeast extracts 0.094%, glucose 0.101% and Tween 80 0.080%. Using the medium obtained, about 1,220 mg l(-1) of nicotine was degraded (95.55%) within 10 h at the specific biodegradation of 116.59 mg l(-1) h(-1) in 30-l bioreactor containing 25-l tobacco extract. CONCLUSIONS: An optimal medium of nicotine degradation by the strain DN2 was obtained. SIGNIFICANCE AND IMPACT OF THE STUDY: RSM proved to be reliable in developing the model, optimizing factors and analysing interaction effects. The results provide better understanding on the interactions between yeast extract, glucose and Tween 80 for nicotine biodegradation.     

Administration of a novel plant extract product via drinking water to post-weaning piglets: effects on performance and gut health

The present study evaluated the effects of a novel plant extract (PE) product (Grazix^TM) on the performance and gut health of weaned piglets challenged with Escherichia coli. The PE was a standardised mixture of green tea leaves (Camellia sinensis) and pomegranate fruit (Punica granatum) obtained by using the LiveXtract^TM process. A total of 144 piglets were weaned at 24 days and allocated to 8 for a 35-day experiment with a 2×2×2 factorial design comparing different treatments (water without product (CT) or 8 μl/kg per day PE in drinking water (PE)), feeding regimens (ad libitum (AD) or restricted (RE)) and oral E. coli challenges on day 9 (sham (−) or infected (+)). There were six pens per group with three piglets per pen. On day 35, 24 of the RE feeding piglets were slaughtered. It was found that PE supplementation increased the average daily gain (ADG) from day 28 to day 35 (P=0.03) and increased the gain to feed ratio (G : F) from day 7 to day 14 (P=0.02). RE feeding led to lower feed intake in piglets during the 1^st week (P<0.01), 2^nd week (P=0.06), 3^rd week (P=0.05), and throughout the course of the overall study period (P=0.05). E. coli challenge decreased the ADG and G : F ratio from day 7 to day 14 (P=0.08 and <0.01, respectively) and increased the faecal score (higher values indicate more severe diarrhoea) on days 14, 21, 28 and 35 (P<0.01). PE supplementation decreased the faecal score in the challenged piglets during the 1^st week post-challenge (P<0.01). E. coli challenge increased the faecal E. coli level on day 14 (P=0.03) and increased the Enterobacteriaceae level on day 35 (P<0.01). Reduced faecal E. coli was observed on days 14 and 35 (P=0.05 and 0.02, respectively), and reduced Enterobacteriaceae (P<0.01) was found on day 35 in the PE animals. RE feeding increased the faecal Lactobacillus, Enterobacteriaceae and E. coli levels on day 35 (P=0.02, <0.01 and <0.01, respectively). These results suggest that PE supplementation may improve the gut health status of post-weaning piglets and counteract some of the negative effects that occur when piglets are challenged with E. coli.     

Impact of Acacia bark extract tablets on the skin of healthy humans: a randomized,double-blind,placebo-controlled study

This study investigated the effects of proanthocyanidins derived from Acacia (Acacia mearnsii) bark extract in healthy Japanese adult subjects experiencing uncomfortable skin symptoms. All subjects were randomly allocated into two groups (n = 33 each) using a computerized random-number generator. The subjects received either Acacia bark extract tablets or placebo for 8 weeks. Evaluations included water content in the stratum corneum, transepidermal water loss (TEWL), Skindex-16, dermatology life quality index (DLQI), visual analog scale for desire to scratch, and blood tests. At 4 weeks, the symptom/feeling score of DLQI, subjective symptoms related to uncomfortable skin, and the desire to scratch were significantly reduced in the intervention group than in the placebo group. At 8 weeks, the intervention group exhibited significantly lower TEWL on facial skin than that in the placebo group. In conclusion, the intake of Acacia bark extract tablets reduced TEWL and improved dry and uncomfortable skin.