Fractional Factorial Screening Design Research Articles

Shedding light on phototrophic biomass production of Chlorella variabilis: The importance of dissolved CO2, light intensity and duty cycle.

Chlorella variabilis NC64A has recently gathered significant scientific attention due to its unique relationship with the PBCV-1 virus which can potentially simplify downstream processing and reduce associated costs for the bio-production of ethanol or hyaluronan. However, photoautotrophic process optimisation is far from trivial due to the unique characteristics of incident light as a critical process parameter (CPP) and its complex interactions with other CPPs. In the present work, a formalised statistical Design of Experiments (DoE) approach is employed for the multiparametric optimisation of phototrophic growth of C. variabilis in closed, controlled and artificially illuminated batch cultures. Initially, the process design space comprising six CPPs, three related to the quality of incident light and three related to the culture environment, was explored using a fractional factorial screening design. Subsequently, a higher resolution face-centred central composite design involving the three most influential parameters identified from the screening round was used for process optimisation. The optimal growth conditions obtained in the present study (light intensity: 600 µE, spectral composition: white LED, duty cycle: 60%, temperature: 28 °C, pH: 7.1, dissolved inorganic carbon [DIC]: 16.3 mM) resulted in a biomass concentration of 0.749 g/L which represents a 70% increase compared to previously reported efforts.

Setting up a diagram process for the elaboration of a new plant‐based beverage from Pinus halepensis seeds: Selection of unit operations and their conditions

AbstractAleppo pine seeds are a potential candidate for the production of nondairy milk due to their high protein (26%) and lipid (37%) content and their availability. For the first time, this study presents the implementation of a manufacturing scheme from seeds to final product, including pre‐extraction, extraction, and post‐extraction (physical and microbiological stabilization), using a 2(7‐4) fractional factorial screening design. The seven factors were seed soaking time, grinding time, temperature and seed/water ratio during extraction, xanthan gum concentration, homogenization pressure, and pasteurization temperature. Beverage quality analysis consisted of measurements of chemical composition, color, stability, and rheological behavior. The results of experimental design showed that the dry matter as well as the lipid and protein contents increased significantly by increasing the ratio (grain/water) and the grinding time. On the other hand, the extraction temperature led to a better extraction of lipids but a lower extraction of proteins. Regarding stability, xanthan gum had a negative effect, while homogenization pressure and pasteurization temperature showed their effectiveness in decreasing the particle size and increasing the physical stability of the product.Practical applicationsPlant‐based drinks, also called plant milks, are interesting alternatives to animal milk. They have similar organoleptic properties but are more sustainable and offer very different nutritional composition depending on the plant used. As the consumers demand is constantly increasing, setting up fabrication processes from new plant sources is relevant. Aleppo pine seeds are a potential matrix for the production of vegetable beverages because they are very nutritious and available in the entire Mediterranean area. This study presents the setting up of a fabrication diagram of a plant‐based beverage made from Aleppo pine seeds. Seven production parameters were tested, including pre‐extraction (seed conditioning), extraction, and post‐extraction (physical and microbiological stabilization), thanks to a fractional factorial 2(7‐4) screening design. The best conditions enabled the production of a final beverage comparable to other commercialized plant‐based beverages in terms of nutritional and organoleptic quality.

Evaluation of influential factors in microwave assisted pyrolysis of sugarcane bagasse for biochar production

Microwave assisted pyrolysis (MAP) is an efficient technology for the production of biochar. However, its large-scale application is limited due to lack of process optimization resulting in lower yield. Identification of significantly influencing parameters is essential for efficient optimization. Thus, in present study, screening of factors like the feedstock amount, feedstock size, moisture content, catalyst dosage, microwave power and exposure time using half fractional factorial screening design was done to identify the most influencing factor affecting sugarcane bagasse biochar yield. The formulated linear model was found to be significant with a regression coefficient ( R 2 ) of 0.9365. Half normal plot and the Pareto chart analysis showed that MAP to be mostly influenced by feedstock amount, microwave irradiation time, feedstock size and microwave power. Maximum biochar yield of 44.46% was obtained with 10 g feedstock (0.015 cm) at 720 W after 20 min, which would be optimized further to improvise the process efficiency. • Microwave power and time shows prominent impact on biochar yield. • Appropriate moisture content facilitates better microwave assisted pyrolysis. • Maximum biochar yield of 44.46% was obtained under optimal conditions. • Microwave biochar shows good porous characteristics and fixed carbon.

Fabrication and characterization of coblended methyl cellulose with polyvinyl alcohol electrospun nanofibers as a carrier for drug delivery system

Polymeric nanofibers have gained a great deal of attention in recent years. This study aims to produce and evaluate a methylcellulose (MC) and polyvinyl alcohol (PVA) based nanofibers mat using the electrospinning process. 25–2 fractional factorial screening design has been used to study the effect of critical formulation and process parameters, such as concentration of MC (%), the concentration of PVA (%), applied Voltage (kV), distance (cm), flow rate (ml/hr) on the critical quality attributes like fiber diameter, tensile strength, and morphology. The fiber morphology and fiber diameter of nanofibers were investigated by scanning electron microscopy (SEM).s The optimized nanofibers mat was further characterized by Fourier transform infrared (FTIR) spectroscopy, Differential scanning electrons (DSC), Thermal gravimetric analysis (TGA), X-ray diffraction (XRD), Atomic force microscopy (AFM). Parameters such as contact angle and rate of biodegradation were studied for an optimized batch. The SEM results showed the uniform morphology of optimized nanofibers without beads with fiber diameter in the range of 100–200 nm. FTIR analysis demonstrated good intermolecular interactions between the molecules of MC with PVA. DSC-TGA study showed good thermal properties of nanofibers. XRD study showed the crystalline nature of nanofibers. Maximum tensile strength up to 2.74 Mpa was obtained which is desired for drug delivery application. The exaggeration of the fiber diameter was measured by AFM and found good surface morphology. Furthermore, results of contact angle and biodegradation rate proved that prepared nanofibers would be considered as a suitable carrier for controlled drug delivery applications like wound healing.

Clarithromycin Solid Lipid Nanoparticles for Topical Ocular Therapy: Optimization, Evaluation and In Vivo Studies.

Solid lipid nanoparticles (SLNs) are being extensively exploited as topical ocular carrier systems to enhance the bioavailability of drugs. This study investigated the prospects of drug-loaded SLNs to increase the ocular permeation and improve the therapeutic potential of clarithromycin in topical ocular therapy. SLNs were formulated by high-speed stirring and the ultra-sonication method. Solubility studies were carried out to select stearic acid as lipid former, Tween 80 as surfactant, and Transcutol P as cosurfactant. Clarithromycin-loaded SLN were optimized by fractional factorial screening and 32 full factorial designs. Optimized SLNs (CL10) were evaluated for stability, morphology, permeation, irritation, and ocular pharmacokinetics in rabbits. Fractional factorial screening design signifies that the sonication time and amount of lipid affect the SLN formulation. A 32 full factorial design established that both factors had significant influences on particle size, percent entrapment efficiency, and percent drug loading of SLNs. The release profile of SLNs (CL9) showed ~80% drug release in 8 h and followed Weibull model kinetics. Optimized SLNs (CL10) showed significantly higher permeation (30.45 μg/cm2/h; p < 0.0001) as compared to control (solution). CL10 showed spherical shape and good stability and was found non-irritant for ocular administration. Pharmacokinetics data demonstrated significant improvement of clarithromycin bioavailability (p < 0.0001) from CL10, as evidenced by a 150% increase in Cmax (~1066 ng/mL) and a 2.8-fold improvement in AUC (5736 ng h/mL) (p < 0.0001) as compared to control solution (Cmax; 655 ng/mL and AUC; 2067 ng h/mL). In summary, the data observed here demonstrate the potential of developed SLNs to improve the ocular permeation and enhance the therapeutic potential of clarithromycin, and hence could be a viable drug delivery approach to treat endophthalmitis.

Genotypic and phenotypic diversity among Lactobacillus plantarum and Lactobacillus pentosus isolated from industrial scale cucumber fermentations

The Lactobacillus plantarum and Lactobacillus pentosus genotypes existing in industrial-scale cucumber fermentations were defined using rep-PCR-(GTG)5. The ability of each genotype to ferment cucumbers under various conditions was evaluated. Rep-PCR-(GTG)5 was the technique capable of illustrating the most intraspecies discrimination compared to the sequencing of housekeeping genes (recA, dnaK, pheS and rpoA), MLST and RAPD with primers LP1, OPL5, M14 and COC. Ten genotypic clusters were defined for the 199 L. pentosus tested and three for the 17 L. plantarum clones. The ability of the 216 clones genotyped and 37 additional cucumber fermentation isolates, of the same species, to rapidly decrease the pH of cucumber juice medium under various combinations of sodium chloride (0 or 6%), initial pH (4.0 or 5.2) and temperatures (15 or 30 °C) was determined using a fractional factorial screening design. A reduced fermentation ability was observed for the L. plantarum strains as compared to L. pentosus, except for clone 3.2.8, which had a ropy phenotype and aligned to genotypic cluster A. L. pentosus strains belonging to three genotypic clusters (B, D and J) were more efficient in cucumber juice fermentation as compared to most L. plantarum strains. This research identified three genetically diverse L. pentosus strains and one L. plantarum as candidates for starter cultures for commercial cucumber fermentations.

Developing an Improved UHPLC Method for Efficient Determination of European Pharmacopeia Process-Related Impurities in Ropinirole Hydrochloride Using Analytical Quality by Design Principles.

This article presents the development of a reversed-phase ultra-high-performance liquid chromatographic method for determining process-related impurities in ropinirole hydrochloride drug substance applying the analytical quality by design approach. The current pharmacopeial method suffers from selectivity issues due to two coelutions of two pairs of impurities. The development of a new method began with preliminary experiments, based on which the Acquity UPLC BEH C8 was selected as the most appropriate column. The effects of six different critical method parameters (CMPs) were then investigated using a fractional factorial screening design. Column temperature, the ratio of methanol in mobile phase B, and gradient slope turned out to be highly significant CMPs in achieving critical resolutions, and they were further evaluated using a central composite face-centered response-surface design. Mathematical models were created by applying a multiple linear regression method. Based on the elution order of an unknown degradation impurity and impurity C, two design spaces were established, and for each design space an optimal combination of CMPs was determined. The method developed was validated for precision, accuracy, linearity, and sensitivity, and it was proven suitable for determining nine process-related impurities of ropinirole.

Optimization of flavonoids extraction from Lippia graveolens and Lippia origanoides chemotypes with ethanol-modified supercritical CO2 after steam distillation

Steam distillation of essential oils from Lippia origanoides K. and Lippia graveolens K. leaves plant material residues that can be valorized. Flavonoids can be selectively extracted from these substrates using ethanol-modified supercritical CO2, as attempted in this work. The thymol-rich L. origanoides chemotype was used to test extraction reproducibility. The effects of pressure, temperature, time, CO2 mass flow, particle size, and percent ethanol on the extraction yield of oleoresin and flavonoids were examined with a 2(6−2) fractional factorial screening design. The variables with a significant influence on yields (pressure, time, CO2 mass flow, and percent ethanol) were used in a simplex optimization to determine the conditions for maximum extraction from L. graveolens and three L. origanoides chemotypes. The extracts’ flavonoid content was estimated by UV–vis spectroscopy with a multivariate calibration model. UHPLC-ESI(+)-Orbitrap-MS was employed for extract identification and quantification. The extracts from the various plant material residues had qualitative and quantitative differences in flavonoid composition. Under the best extraction conditions found (307 bar, 5 % ethanol, 43 g CO2/min), the steam-distilled plant material from the phellandrene-rich L. origanoides chemotype afforded 4.1 g of pinocembrin per kg of dry substrate. Results of this work facilitate the implementation of supercritical CO2 extraction processes to valorize byproducts of the essential oil industry by obtaining extracts that contain flavonoids.

Chiral separation of lansoprazole and rabeprazole by capillary electrophoresis using dual cyclodextrin systems.

Novel capillary electrophoresis methods using CDs as chiral selectors were developed and validated for the chiral separation of lansoprazole and rabeprazole, two proton pump inhibitors. Fourteen different neutral and anionic CDs were screened at pH 4 and 7 in the preliminary analysis. Sulfobutyl-ether-β-CD with a degree of substitution of 6.5 and 10 at neutral pH proved to be the most suitable chiral selector for both compounds. Various dual CD systems were also compared, and the possible mechanisms of enantiomer separation were investigated. A dual selector system containing sulfobutyl-ether-β-CD degree of substitution 6.5 and native γ-CD proved to be the most adequate system for the separations. Method optimization was carried out using an experimental design approach, performing an initial fractional factorial screening design, followed by a central composite design to establish the optimal analytical conditions. The optimized methods (25mM phosphate buffer, pH 7, 10mM sulfobutyl-ether-β-CD/20mM γ-CD, +20kV voltage; 17°C temperature; 50 mbar/3 s injection, detection at 210nm for lansoprazole; 25mM phosphate buffer, pH 7, 15mM sulfobutyl-ether-β-CD/30mM γ-CD, +20kV voltage; 18°C temperature; 50mbar/3 s injection, detection at 210nm for rabeprazole) provided baseline separation for lansoprazole (Rs = 2.91) and rabeprazole (Rs = 2.53) enantiomers with favorable migration order (in both cases the S-enantiomers migrates first). The optimized methods were validated according to current guidelines and proved to be reliable, linear, precise, and accurate for the determination of 0.15% distomer as chiral impurity in dexlansoprazole and dexrabeprazole samples.

Surface Design of Enantiomeric HPLC Separation on Vancomycin and Teicoplanin-Based Stationary Phases, a Tool for Chiral Recognition of Model β-Blockers.

A quality-by-design approach was adopted for enantioseparation of atenolol on Vancomycin and Teicoplanin-based chiral stationary phases using reversed phase (RP) mode and polar ionic mode (PIM), respectively to account for major forces involved in enantiorecognition of β-blockers on macrocyclics. A fractional factorial screening design for the two modes; followed by a central composite optimization design and regression analysis were able to point out critical factors and chromatographic responses and robust surface of the design. Within the studied range of flow the optimal was 0.3 mL/min for Chirobiotic T and 1 mL/min for Chirobiotic V. In PIM, a composition of 100% methanol was mandatory to compromise between best separation and least retention with equal amounts of the acid and base modifiers for enantiomers of atenolol, as model drug in addition to metoprolol and pindolol as structurally related compounds for possible extrapolation of results on members of the same class. However, in RP mode, only triethylamine acetate was needed as buffer for atenolol enantiomers. Chiral recognition of atenolol in both elution modes, further confirmed via extrapolation of the models on the two other β-blockers showed that ionic interactions rather than any other forces governed chiral recognition on the two macrocyclic stationary phases in both modes.

Assessment of material and process attributes' influence on tablet quality using a QbD and DEM combined approach

The combined approach of quality by design (QbD) framework and discrete element method (DEM) is applied to force feeding process within the tableting machine to assess the influence of potential critical process conditions (CPPs) and critical material attributes (CMAs) on tablet quality. The numerical model considers the three paddled force feeder of a FETTE 1200i tableting machine. The influence of the selected potential CPPs: turret speed and paddle wheels speed and CMAs: API dose strength, inter-particle cohesion, and particle-wall friction on the critical quality attributes (CQAs) tablet mass, tablet mass variation, and content uniformity are evaluated by using a fractional-factorial screening design. In addition to the CQAs, the DEM provides the opportunity to shed light on the powder flow phenomena within the force feeder thus an understanding on the impact of the paddle wheels on powder over-lubrication and particle attrition is provided. Such a combined approach of QbD and DEM helps in identifying the significance of selected CPPs and CMAs and thereby to generate the design space providing an optimal tablet quality.

Optimization of Medium Components for the Production of Antagonistic Lytic Enzymes Against Phytopathogenic Fungi and Their Biocontrol Potential

In this paper, fractional factorial screening design (FFSD) and central composition design (CCD) were used to optimize the medium components for producing chitinase and gelatinase by Lysobacter capsici YS1215. Crab shell powder, nutrient broth and gelatin were proved to have significant effects on chitinase and gelatinase activity by FFSD first. An optimal medium was obtained by using a three factor CCD, which consisted of nutrient broth of <TEX>$2.0gL^{-1}$</TEX>, crab shell powder of <TEX>$2.0gL^{-1}$</TEX> and gelatin of <TEX>$1.0gL^{-1}$</TEX>, respectively with the highest chitinase activity (<TEX>$3.34UmL^{-1}$</TEX>) and gelatinase activity (<TEX>$14.15UmL^{-1}$</TEX>). This value was 3.76 and 1.11 fold of the chitinase and gelatinase activity, respectively, compared to the lowest productive medium in the design matrix. In investigating potential of these enzymes partially purified from L. capsici YS1215 for biotechnological use, the crude enzymes was found to be inhibition against pathogenic fungal mycelia: Colletotrichum gleosporioides, Phytophthora capsici, and Rhizoctonia solani. In this study, we demonstrated the optimal medium for producing the chitinolytic and gelatinolytic enzymes by the strain YS1215 and the role of their enzymes that may be useful for further development of a biotechnological use and agricultural use for biological control of phytopathogenic fungi.

UPLC Method for Determination of Moxonidine and Its Degradation Products in Active Pharmaceutical Ingredient and Pharmaceutical Dosage Form

A simple, rapid, isocratic, stability-indicating reverse phase ultra-performance liquid chromatographic (RP-UPLC) method was developed and validated for the routine analysis of moxonidine in the presence of its degradation products in active pharmaceutical ingredient and pharmaceutical dosage forms. Forced degradation studies were performed according to the guidance of International Conference for Harmonization and were used to evaluate moxonidine intrinsic stability. The drug was subjected to acid, neutral and base hydrolysis as well as to oxidative, thermal and photolytic decomposition in both solution and solid state. The drug appeared to be unstable towards acid and base hydrolysis. To achieve desirable conditions for UPLC analysis, the method development was done with the assistance of experimental design and multivariate optimization methodology by means of Derringer’s desirability function. Stress samples were analyzed according to the experimental plan for fractional factorial screening design and Box-Behnken optimization design. The chromatographic separation was achieved on a C18 Hypersil Gold aq. column (100 mm × 2.1 mm, 1.9 μm) with the mobile phase consisting of methanol–ammonium acetate buffer (10 mM, pH 3.43) mixture (0.9:99.1, v/v) pumped at a flow rate of 870 μL min−1 and detection wavelength of 255 nm. The UPLC–MS and UPLC–MS/MS analyses were further used to characterize the found degradation products. The validation of the proposed method was also performed considering selectivity, linearity, accuracy, precision, limit of detection and limit of quantification, and the results indicated that the method fulfilled all required criteria. The method was successfully applied to the analysis of commercial tablets.

Optimization of a refolding step for a therapeutic fusion protein in the quality by design (QbD) paradigm

Production of biotech therapeutics in Escherichia coli involves protein expression as insoluble inclusion bodies that need to be denatured and the resulting protein refolded into the native structure. In this paper, we apply a Quality by Design approach using Design of Experiments for optimization of the refolding process for a recombinant biotech therapeutic, granulocyte colony stimulating factor. First, risk analysis was performed to identify process parameters that require experimental examination. Next, the chosen parameters were examined using a fractional factorial screening design. Based on the results of this study, parameters that have significant effect on refold yield and product quality were identified and examined using a full factorial Design of Experiments for their interactions. The final model was statistically significant and delivered a refolding yield of 77%. Further, kinetics of refolding was evaluated under optimal conditions and was found to be of first order with a rate constant of 0.132/min. Design space was established for the three parameters for a given permissible range of yield, protein concentration, and purity. The primary objective of this paper is to provide a roadmap for implementing Quality by Design for development of a protein refolding step.

Semi-Continuous Emulsion Copolymerization of Styrene-Butyl Acrylate with Methacrylic Acid: Screening Design of Experiments

A fractional factorial screening design of experiments was conducted to identify the effects of five variables, i.e., styrene/butyl acrylate ratio, methacrylic acid content, pH, emulsifier content, and chain transfer agent content on various product properties in the monomer-starved semi-batch emulsion copolymerization of styrene/butyl acrylate. The impact of these variables on the methacrylic acid (MAA) distribution in the latex, the average latex particle diameter, the molecular weight and distribution of the polymer products, the glass transition temperature (Tg) of the polymer, and the coating adhesion to a plastic substrate was studied.

Stochastic analysis of dynamic interaction between train and railway turnout

The performance of a railway turnout (switch and crossing) is influenced by a large number of input parameters of the complex train–turnout system. To reach a robust design that performs well for different traffic situations, random distributions (scatter) of these inputs need to be accounted for in the design process. Stochastic analysis methods are integrated with a simulation model of the dynamic interaction between train and turnout. For a given nominal layout of the turnout, using design of experiments methodology and a two-level fractional factorial screening design, four parameters (axle load, wheel–rail friction coefficient, and wheel and rail profiles) are identified to be the most significant. These parameters are further investigated using a three-level full factorial design and stochastic analysis. The random distributions of transverse wheel profile and set of transverse rail profiles along the switch panel are accounted for by the Karhunen–Loève expansion technique. The influence of the random distributions of the input parameters on the statistical outputs of wheel–rail contact forces, wear and rolling contact fatigue is assessed using Latin hypercube sampling to generate a number of stochastic load realizations.

A novel approach to develop β-galactosidase entrapped in liposomes in order to prevent an immediate hydrolysis of lactose in milk

A fractional factorial screening design and a response surface methodology were applied to optimize the entrapment of β -galactosidase in liposomes by dehydration-rehydration vesicle method. The effect of lipid (phosphatidylcholine and cholesterol), enzyme concentration, buffer pH, type and time of sonication, and sucrose concentration were the parameters selected for this study. The cholesterol:phosphatidylcholine (Ch:PC) ratio was the most important factor followed by type of sonicator and enzyme:lipid (E:L) ratio. The buffer pH, sucrose concentration and sonication time did not play an important role in the response. Two of the factors (Ch:PC and E:L ratios) were further studied in a 3 2 central composite design. The optimized liposomal formulation with an entrapment efficiency of 28% was obtained with Ch:PC and E:L ratios of 0.53 and 13.76, respectively, at pH 6 and employing a probe type sonicator.

Formulation and characterisation of primaquine loaded liposomes prepared by a pH gradient using experimental design

The effect of different formulation factors (lipid type, cholesterol, charge, internal buffer capacity, drug-to-lipid incubation ratio) on the encapsulation efficiency and size of primaquine liposomes (SUV's) in response to a pH gradient was investigated by a fractional factorial screening design. Three of the factors (charge, internal buffer capacity, drug-to-lipid incubation ratio) were further studied in a Box–Behnken optimisation design. The lipid type was the most important parameter followed by the drug-to-lipid incubation ratio, buffer capacity, cholesterol and charge. Several of the interactions were important. In the optimisation design a robust region with high encapsulation efficiency (>95%) was obtained for DSPC: 33.33 mol% cholesterol-liposomes at high internal citrate concentration (200 mM) by maintaining the drug-to-lipid incubation ratio below 0.15:1 (mol:mol) and varying the charge incorporation between 2 and 10%. In order to achieve long-term stability and sterility, the liposomes were lyophilised followed by gamma irradiation. The pH gradient was maintained during this treatment with little chemical degradation of the substances. The final preparation consisted of three separate vials with lyophilised liposomes, solid state primaquine and hydration medium.

Critical Dissolution Tests of Oral Systems Based on Statistically Designed Experiments. IH. In Vitro/In Vivo Correlation for Multiple-Unit Capsules of Paracetamol Based on PLS Modeling

The main aims of the present study were to establish an in vitro/in vivo correlation/or multiple-unit capsules of paracetamol by means of statistical prediction models and to investigate the effect of a number of in vitro variables on the discussion rate of paracetamol from the formulation. A fractional factorial screening design was used to investigate the effects of the variables agitation, pH, osmolality, viscosity, and the presence of bile salt on the dissolution rate of paracetamol. The effects were evaluated in two separate partial least-squares models, in which the responses were expressed as the cumulative percentage of paracetamol dissolved at specified time-points (model I) and as the shape (β) and scale (η) parameters according to the Weibull function (model II).It was concluded that agitation and viscosity had significant effects on the dissolution rate of paracetamol. Statistical models based on the responses from models I and II were then used to predict the in vitro conditions most closely correlated with the in vitro dissolution of paracetamol after administration of the formulation to 10 healthy volunteers. The predicted optimal in vitro conditions were similar for the two models and not too far from what is expected from the gastrointestinal tract. The experimental verification of the in vitro conditions showed that both models were equally good, and contributed to high degrees of correlation with the in vivo dissolution behavior of the formulation during 9 hr. The relationships obtained when plotting the percentage dissolved in vitro versus in vivo were y - 1.1x (r2 = 0.98) and y = 1.1x (r2 = 0.94) for models I and II, respectively. Based on these results, it is difficult to state a preference for one of the models. Finally, the use of statistical prediction models to develop critical in vitro tests is a successful approach in the establishment of associations between dissolution behavior in vitro and in vivo for oral extended-release systems.

The application of experimental design to the robustness testing of a method for the determination of drug-related impurities by capillary electrophoresis

Robustness testing of capillary electrophoresis methods is an important part of method validation. Appropriate use of experimental designs can be employed in this robustness testing. In this study experimental designs were used in the assessment of a capillary electrophoresis method used to determine drug related impurities. Initially a fractional factorial screening design was used to identify the critical parameters which were found to be pH and voltage. A central composite design was then performed to evaluate the response surfaces for pH and voltage which showed operation at the optimum pH and voltage values.