Experimental Design in Method Optimization and Robustness Testing

Dejaegher, Bieke; Durand, Alexandra; Heyden, Yvan Vander

doi:10.1002/9780470530191.ch2

Cited by 10 publications

(36 citation statements)

References 91 publications

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“…(1) (2) in which ΣY(1), ΣY(0), and ΣY(-1) represent the sum of the responses (resolution between enantiómeros, Rs) where the factors x (CD type, % CD, pH and % MeOH) are at level 1, 0 and -1, respectively (Table 1), with "N" representing the number of design experiments [29,[31][32] for a 3 levels, 4 factors fractional factorial design (3 4-2 ) used here N= 9 experiments. The aim of this evaluation is to select the experimental conditions that lead to the best separation (i.e.…”

Section: Calculationsmentioning

confidence: 99%

Molecular Modeling and Chiral Separation of Benzodiazepines by Capillary Electrophoresis Using Highly Sulfated Cyclodextrins

Martinez

Galicia

2018

J. Mex. Chem. Soc.

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<p>A capillary electrophoretic method for the chiral separation of the 3-chiral-1,4-benzodiazepines was developed. Enantiomeric resolution of oxazepam, lorazepam, temazepam, and lormetazepam was achieved using sulfated cyclodextrins (CD's) as chiral selectors. A 3-levels, 4-factors fractional factorial (34-2) design was applied to test 3 different CD's: heptakis-6-sulfato--cyclodextrin (HSCD), heptakis-(2,3-diacetyl-6-sulfato)--cyclodextrin (HDASCD), and heptakis-(2,3-dimethyl-6-sulfato)--cyclodextrin (HDMSCD). The CD type, its concentration, the pH of the electrolyte, and % organic modifier were tested as the factors in the experimental design. The highest resolution values were obtained using a 20 mM borate buffer, pH 9.0 with the addition of 5 % HSCD and 15 % methanol as an organic modifier. At these separation conditions, the equilibrium constants of the benzodiazepine-HSCD complex formation were calculated. A theoretical study of the interaction benzodiazepine-HSCD complex using semiempirical calculations is postulated.</p>

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Section: Calculationsmentioning

confidence: 99%

Molecular Modeling and Chiral Separation of Benzodiazepines by Capillary Electrophoresis Using Highly Sulfated Cyclodextrins

Martinez

Galicia

2018

J. Mex. Chem. Soc.

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“…CE is suitable for the use of experimental design in which the experimental conditions could be varied from one experiment to another. Up to date, there are only a few studies that report the use of experimental designs in the field of chiral enantioseparation in CE . The separation strategies are therefore valuable since they should propose a limited set of experimental conditions, which maximize the probability to separate numerous pharmaceuticals with different molecular structures and properties .…”

Section: Introductionmentioning

confidence: 99%

A chiral enantioseparation generic strategy for anti‐Alzheimer and antifungal drugs by short end injection capillary electrophoresis using an experimental design approach

2017

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The present study describes a generic strategy using capillary electrophoretic (CE) method for chiral enantioseparation of anti-Alzheimer drugs, namely, donepezil (DON), rivastigmine (RIV), and antifungal drugs, namely, ketoconazole (KET), Itraconazole (ITR), fluconazole (FLU), and sertaconazole (SRT) in which these drugs have different basic and acidic properties. Several modified cyclodextrins (CDs) were applied for enantioseparation of racemates such as highly sulfated α, γ CDs, hydroxyl propyl-β-CD, and Sulfobutyl ether-β-CD. The starting screening conditions consist of 50-mM phosphate-triethanolamine buffer at pH 2.5, an applied voltage of 15 kV, and a temperature of 25°C. The CE strategy implemented in the separation starts by screening prior to the optimization stage in which an experimental design is applied. The design of experiment (DOE) was based on a full factorial design of the crucial two factors (pH and %CD) at three levels, to make a total of nine (3 ) experiments with high, intermediate, and low values for both factors. Evaluation of the proposed strategy pointed out that best resolution was obtained at pH 2.5 for five racemates using low percentages of HS-γ-CD, while SBE-β-CD was the most successful chiral selector offering acceptable resolution for all the six racemates, with the best separation at low pH values and at higher %CD within 10-min runtime. Regression study showed that the linear model shows a significant lack of fit for all chiral selectors, anticipating that higher orders of the factors are most likely to be present in the equation with possible interactions.

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“…QbD has become a significant model for the pharmaceutical industries and defined in the International Conference on Harmonization (ICH) regulation on pharmaceutical development as ''a systematic approach to the development that begins with predefined objectives and emphasizes product and process understanding and process control, based on sound science and quality risk management.'' [2] For method optimization, either sequential optimization methods, using simplex approaches, [3,4] or simultaneous optimization strategies, using response-surface designs, [4][5][6] are reported. The main difference between their applications is that for a response-surface design the experimental design domain, defined by the factor levels examined, is expected to contain the optimum, whereas a sequential optimization method can be applied in situations where the experimental domain containing the optimum result is not previously known.…”

Section: Introductionmentioning

confidence: 99%

Development of a New High-Performance Thin Layer Chromatographic Method for Quantitative Estimation of Lamivudine and Zidovudine in Combined Tablet Dosage Form Using Quality by Design Approach

Gopani¹,

Patel²,

Patel

et al. 2014

Journal of Liquid Chromatography & Related Technologies

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& The purpose of this study was to develop a new rapid and robust high-performance thin layer chromatographic (HPTLC) method for separation and quantitation of lamivudine and zidovudine in combined tablet dosage form using a quality by design approach. A Box-Behnken experimental design with response surface methodology was utilized to study the effects of chromatographic chamber saturation time, mobile phase migration distance, and mobile phase composition on R f value. The R f value was predicted for lamivudine and zidovudine in between 0.2 and 0.8 to optimize the chromatographic conditions based on the preliminary trials. The optimized chromatographic conditions were 21 min saturation time, 50 mm migration distance, and ethyl acetate:hexane:methanol:acetic acid (4:4:2:0.1 v=v=v=v) as a mobile phase. The optimized HPTLC method was validated according to International Conference on Harmonization (ICH) guideline Q2 (R1). The results of study clearly indicate that quality by design concept could be effectively applied to optimize HPTLC method with the minimum number of experimental runs. Developed HPTLC method was successfully applied for routine analysis of lamivudine and zidovudine in combine tablet dosage form.

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Experimental Design in Method Optimization and Robustness Testing

Cited by 10 publications

References 91 publications

Molecular Modeling and Chiral Separation of Benzodiazepines by Capillary Electrophoresis Using Highly Sulfated Cyclodextrins

Molecular Modeling and Chiral Separation of Benzodiazepines by Capillary Electrophoresis Using Highly Sulfated Cyclodextrins

A chiral enantioseparation generic strategy for anti‐Alzheimer and antifungal drugs by short end injection capillary electrophoresis using an experimental design approach

Development of a New High-Performance Thin Layer Chromatographic Method for Quantitative Estimation of Lamivudine and Zidovudine in Combined Tablet Dosage Form Using Quality by Design Approach

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