• Title/Summary/Keyword: Box-behnken method

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Increased Alkaline Protease Production from Bacillus clausii I-52 by Experimental Design Methods (통계학적 방법을 이용한 Bacillus clausii I-52로부터 염기성 단백질 분해효소 생산 증진)

  • Lee Jae-woo;Kim Hyun-soo;Chang Chung-soon;Kim Eun-ki
    • KSBB Journal
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    • v.20 no.3
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    • pp.215-219
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    • 2005
  • Production of alkaline pretense by Bacillus clausii I-52 was optimized by experimental design methods. Among 7 medium components, three (wheat flour, sodium citrate, sodium carbonate) were selected as components affecting the pretense activity significantly by Plackett-Burman methods. Furthermore the ranges of effective concentrations were determined by Box-Behnken methods. The objective function describing the alkaline pretense production was obtained and optimum concentration of 3 components was determined by using response-surface methods (RSM). Theoretical maximum production was 74000 U/mL (Wheat flour: 0 g/L, Sodium citrate: 5 g/L, Sodium carbonate: 10 g/L). With the optimized medium composition, 92000 U/mL alkaline protease was produced experimentally, resulting in $90\%$ increase compared to before-optimization production (49000 U/mL).

Optimization of the experimental conditions for determination of roxithromycin in bulk and dosage forms

  • Jeong, Kyung Min;Lee, Cheong Hoon;Kim, Su Hyun;Lee, Jeongmi
    • Analytical Science and Technology
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    • v.30 no.1
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    • pp.39-48
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    • 2017
  • Roxithromycin (RXT), which is an antibiotic used to treat respiratory tract and urinary infections, is official in Korean Pharmacopoeia (KP) and is marketed in various dosage forms including tablet, granule, suspension, and tablet for suspension in Korea. This study presents how a universal and reliable method to quantify RXT in bulk drug and formulations was developed. Effects of factors including column type, buffer concentration, type and concentration of organic solvent, buffer pH, and type and concentration of mobile phase additive, were examined, and some categorical or crucial factors including the types of column, organic solvent, mobile phase additive and the buffer pH were optimized by one-factor-at-a-time approach. Subsequently, concentrations of the buffer and additive and column temperature were optimized by response surface methodology using Box-Behnken design aiming to acquire the RXT peak of good shape. The optimized method employed a Phenomenex Gemini $5{\mu}$ C18 110A ($150{\times}4.60mm$, $5{\mu}m$) maintained at $30^{\circ}C$ with the mobile phase consisting of 25 mM phosphate buffer (pH 6.0) with 0.3 % tetrabutylammonium hydroxide and methanol at a ratio of 37:63 (v/v). Method validation results showed that the developed method was linear, precise, and accurate. Compared to the compendial methods in KP 10 that exhibited a significant tailing of the RXT peak despite using unfavorably high buffer concentrations and were not harmonized among bulk drug and formulations, this method could be universally applied to RXT bulk drug and marketed products in various dosage forms and thus was adopted in KP 11.

A Dilute-and-Shoot LC-MS/MS Method for Screening of 43 Cardiovascular Drugs in Human Urine

  • Pham, Thuy-Vy;Lee, Gunhee;Mai, Xuan-Lan;Le, Thi-Anh-Tuyet;Nguyen, Thi Ngoc Van;Hong, Jongki;Kim, Kyeong Ho
    • Mass Spectrometry Letters
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    • v.12 no.1
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    • pp.1-10
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    • 2021
  • A simple, specific, and economical LC-MS/MS method was investigated for the screening of 43 prescribed antihypertensive and related drugs in human urine. The urine samples were simply prepared by diluting and mixing with internal standard before directly introduced to the LC-MS/MS system, which is fast, straightforward, and cost-effective. Fractional factorial, Box-Behnken, and I-optimal design were applied to screen and optimize the mass spectrometric and chromatographic factors. The analysis was carried out on a triple quadrupole mass spectrometer system utilizing multiple reaction monitoring with positive and negative electrospray ionization method. Chromatographic separation was performed on a Thermo Scientific Accucore RP-MS column (50 × 3.0 mm ID., 2.6 ㎛) using two separate gradient elution programs established with the same mobile phases. Chromatographic separation was performed within 12 min. The optimal method was validated based on FDA guideline. The results indicated that the assay was specific, reproducible, and sensitive with the limit of detection from 0.1 to 50.0 ㎍/L. The method was linear for all analytes with coefficient of determination ranging from 0.9870 to 0.9981. The intra-assay precision was from 1.44 to 19.87% and the inter-assay precision was between 2.69 and 18.54% with the recovery rate ranges from 84.54 to 119.78% for all drugs measured. All analytes in urine samples were stable for 24 h at 25℃, and for 2 weeks at -60℃. The developed method improves on currently existing methods by including larger number of cardiovascular medications and better sensitivity of 12 analytes.

Optimization of Silver Nanoparticles Synthesis through Design-of-Experiment Method (실험계획법을 활용한 은 나노 입자의 합성 및 최적화)

  • Lim, Jae Hong;Kang, Kyung Yeon;Im, Badro;Lee, Jae Sung
    • Korean Chemical Engineering Research
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    • v.46 no.4
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    • pp.756-763
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    • 2008
  • The aim of this work was to obtain uniform and well-dispersed spherical silver nanoparticles using statistical design-of-experiment methods. We performed the experiments using 2 k fractional factorial designs with respect to key factors of a general chemical reduction method. The nanoparticles prepared were characterized by SEM, TEM and UV-visible absorbance for particle size, distribution, aggregation and anisotropy. The data obtained were analyzed and optimized using a statistical software, Minitab. The design-of-experiment methods using quantified data enabled us to determine key factors and appreciate interactions between factors. The measured properties of nanoparticles were dominated not only by individual one or two main factors but also by interactions between factors. The appropriate combination of the factors produced small, narrow-distributed and non-aggregated silver nanoparticles of about 30 nm with approximately 10% standard deviation.

Optimization of the whole extract of Zarawand Mudaharaj (Aristolochia rotunda L.) root by Response Surface Methodology (RSM)

  • Ansari, MD Zakir;Sofi, Ghulamuddin;Hamiduddin, Hamiduddin;Ahmad, Haqeeq;Basri, Rabia;Alam, Abrar
    • CELLMED
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    • v.11 no.3
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    • pp.15.1-15.9
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    • 2021
  • The chemical constitution of a drug has been accepted as an important basis for pharmacological action in Unani medicine. Various dosage forms have been developed on this concept, such as decoctions (Joshanda), infusions (Khesanda), extract (Rub / Usara), and syrup. Zarawand Mudaharaj (ZM.) / Aristolochia rotunda L. root was subjected to extraction process using Soxhlet's apparatus by using Response Surface Methodology (RSM) to design the number of random runs of the extracts with variation in the factors of temperature, the concentration of ethanol in water, time for extraction, for optimizing and maximizing the yield concentration. The data obtained, was analyzed with regression equation and ANOVA two-way summary to interpret the interaction of the factors for yield maximization. Minitab version 18 was used to design and analyze data. Validation of the optimum conditions for maximum yield of the whole extract of ZM. Root was carried out by re-run of the extract using the optimized conditions. The maximum yield percentage thus obtained using RSM was 20.87% whereas using these optimum conditions 21.35 % yield was obtained thereby validating the method. The association between the response functions and the process variables was identified by a three-factor recorded Box-Behnken design. In the present study RSM is used because itis a cheap and affordable method to optimize maximum yield percentage which may be reliably used by researchers. The study set in the surface conditions for ZM. root extraction by the Soxhlet apparatus for maximizing the yield percentage.

Mechanical, rheological, and durability analysis of self-consolidating concretes containing recycled aggregates

  • Hiwa Mollaei;Taleb Moradi Shaghaghi;Hasan Afshin;Reza Saleh Ahari;Seyed Saeed Mirrezaei
    • Structural Engineering and Mechanics
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    • v.88 no.2
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    • pp.141-157
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    • 2023
  • In the present paper, the effect of recycled aggregates on the rheological and mechanical properties of self-consolidating concrete is investigated experimentally and numerically. Hence, the specimen with two types of recycled aggregates, i.e., known and unknown resistance origins, are utilized for the studied specimens. The experiments in this study are designed using the Box-Behnken method, which is one of the response surface methods. Input variables in mixtures include silica fume in the range of 5-15% as a percentage substitute for cement weight and recycled coarse and fine aggregates in the range of 0-50% for both series of recycled materials as a substitute for natural materials. The studied responses are slump flow, V funnel, compressive strength, tensile strength, and durability. The results indicate that the increase in the amount of recycled aggregates reduces the rheological and mechanical properties of the mixtures, while silica fume effectively improves the mechanical properties. In addition, the results demonstrate that the fine recycled aggregates affect the total response of the concrete significantly. The results of tensile and compressive strengths indicate that the mixtures including 50% recycled materials with known resistance origin demonstrate better responses up to 8 and 10% compared to the materials with unknown resistance origins, respectively. Recycled materials with a specific resistance origin also show better results than recycled materials with an unknown resistance origin. Durability test results represent those concretes containing recycled coarse aggregates have lower strength compared to recycled fine aggregates. Also, a series of mathematical relationships for all the responses are presented using variance analysis to predict mixtures' rheological and mechanical properties.

Evaluation Model of Optimal Operating Conditions for Aquaponics Pretreatment Using Response Surface Methodology (반응표면법을 이용한 아쿠아포닉스 전처리조 최적 운전 조건 평가 모델)

  • Jisoo Kim;Geounwoo Park;Jinseo Choi;Jeonghwan Park
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.57 no.1
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    • pp.32-40
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    • 2024
  • The aim of this research was to apply a method designed to derive the factors influencing total ammonia removal when operating an additional pretreatment system at Aquaponics. The Box-Behnken method, among response surface analysis methods was used to characterize and determine the optimal nitrification conditions when operating the pretreatment system. Among the mathematically and statistically calculated prediction equations, the total ammonia nitrogen concentration Y1 measured on day 8 was derived as Y1=-195.8+2.23X1+42.9X2+47.5X3+0.1856X12-1.380X1X2-1.770X1X3, and the time taken to reach the maximum total ammonia nitrogen concentration during the experiment period was derived as Y2=271-5.04X1+60.5X2-64.8X3+0.1654X12+6.54X32-0.600X1X3-9.00X2X3. The coefficients of determination of the regression models of Y1 and Y2 were 93.99% and 94.46%, respectively. The modified coefficients of determination were also high, at 89.48% and 88.91%, respectively. The prediction coefficients of determination of Y1 and Y2, were 70.68% and 62.11%, respectively, which was relatively lower than that of Y1, but still indicated a reliable prediction performance.

Assessment of statistical sampling methods and approximation models applied to aeroacoustic and vibroacoustic problems

  • Biedermann, Till M.;Reich, Marius;Kameier, Frank;Adam, Mario;Paschereit, C.O.
    • Advances in aircraft and spacecraft science
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    • v.6 no.6
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    • pp.529-550
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    • 2019
  • The effect of multiple process parameters on a set of continuous response variables is, especially in experimental designs, difficult and intricate to determine. Due to the complexity in aeroacoustic and vibroacoustic studies, the often-performed simple one-factor-at-a-time method turns out to be the least effective approach. In contrast, the statistical Design of Experiments is a technique used with the objective to maximize the obtained information while keeping the experimental effort at a minimum. The presented work aims at giving insights on Design of Experiments applied to aeroacoustic and vibroacoustic problems while comparing different experimental designs and approximation models. For this purpose, an experimental rig of a ducted low-pressure fan is developed that allows gathering data of both, aerodynamic and aeroacoustic nature while analysing three independent process parameters. The experimental designs used to sample the design space are a Central Composite design and a Box-Behnken design, both used to model a response surface regression, and Latin Hypercube sampling to model an Artificial Neural network. The results indicate that Latin Hypercube sampling extracts information that is more diverse and, in combination with an Artificial Neural network, outperforms the quadratic response surface regressions. It is shown that the Latin Hypercube sampling, initially developed for computer-aided experiments, can also be used as an experimental design. To further increase the benefit of the presented approach, spectral information of every experimental test point is extracted and Artificial Neural networks are chosen for modelling the spectral information since they show to be the most universal approximators.

Enhanced Production of C30 Carotenoid 4,4'-Diaponeurosporene by Optimizing Culture Conditions of Lactiplantibacillus plantarum subsp. plantarum KCCP11226T

  • Siziya, Inonge Noni;Yoon, Deok Jun;Kim, Mibang;Seo, Myung-Ji
    • Journal of Microbiology and Biotechnology
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    • v.32 no.7
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    • pp.892-901
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    • 2022
  • The rising demand for carotenoids can be met by microbial biosynthesis as a promising alternative to chemical synthesis and plant extraction. Several species of lactic acid bacteria (LAB) specifically produce C30 carotenoids and offer the added probiotic benefit of improved gut health and protection against chronic conditions. In this study, the recently characterized Lactiplantibacillus plantarum subsp. plantarum KCCP11226T produced the rare C30 carotenoid, 4,4'-diaponeurosporene, and its yield was optimized for industrial production. The one-factor-at-a-time (OFAT) method was used to screen carbon and nitrogen sources, while the abiotic stresses of temperature, pH, and salinity, were evaluated for their effects on 4,4'-diaponeurosporene production. Lactose and beef extract were ideal for optimal carotenoid production at 25℃ incubation in pH 7.0 medium with no salt. The main factors influencing 4,4'-diaponeurosporene yields, namely lactose level, beef extract concentration and initial pH, were enhanced using the Box-Behnken design under response surface methodology (RSM). Compared to commercial MRS medium, there was a 3.3-fold increase in carotenoid production in the optimized conditions of 15% lactose, 8.3% beef extract and initial pH of 6.9, producing a 4,4'-diaponeurosporene concentration of 0.033 A470/ml. To substantiate upscaling for industrial application, the optimal aeration rate in a 5 L fermentor was 0.3 vvm. This resulted in a further 3.8-fold increase in 4,4'-diaponeurosporene production, with a concentration of 0.042 A470/ml, compared to the flask-scale cultivation in commercial MRS medium. The present work confirms the optimization and scale-up feasibility of enhanced 4,4'-diaponeurosporene production by L. plantarum subsp. plantarum KCCP11226T.

Optimization of the preparation method of citron (Citrus junos Sieb.) beverage containing hibiscus using response surface methodology (반응표면 분석법을 이용한 히비스커스 첨가 유자 음료 제조의 최적화)

  • Lee, Chang Joo;Lee, Woo Jin;Park, Jong Seok;Kim, Sung Woo;Jung, Sung Keun
    • Korean Journal of Food Science and Technology
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    • v.53 no.2
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    • pp.187-194
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    • 2021
  • This study aimed to optimize the preparation method of citron (Citrus junos Sieb.) beverages with hibiscus using response surface methodology (RSM). The experimental conditions were established using a central composite design with three independent variables as follows: ratios of citron (40~60%), citric acid (0.34~0.94%), and hibiscus (0.3~0.7%). The results indicate that an increase in the citron ratio contributed to increased sweetness and as the concentration of citron and hibiscus increased, the brightness of the citron beverage decreased and the yellowness increased. The citron ratio showed a significant correlation with the ABTS radical scavenging capacity. Among the 15 experimental groups, 4 representative samples showing statistical significance were selected, and sensory tests were performed, in comparison with commercially available products. As a result of the sensory test, four beverages prepared with the selected recipes showed higher preference than commercial beverages, and optimal recipe conditions were 40% citron, 0.34% citric acid, and 0.5% hibiscus.