scholarly journals Analytical Quality by Design as an Important Tool to Determine the Best Analytical Conditions for Isoniazid and Its Respective Succinylated Prodrug

2020 ◽  
Author(s):  
Denise Rampini ◽  
Renan Vinícius de Araújo ◽  
Rodrigo Esteves Foitinho ◽  
Felipe Rebello Lourenço ◽  
Jeanine Giarolla
Keyword(s):  
Flow Rate ◽  
Mobile Phase ◽  
Quality By Design ◽  
Health Concern ◽  
Major Influence ◽  
Analytical Quality ◽  
Pareto Chart ◽  
Test Conditions ◽  
Analytical Test ◽  
The Impact

Abstract Background Tuberculosis is a worldwide health concern and isoniazid is the most used and considered one of the most effective drugs for its treatment. The “quality” concept must be incorporated into the final pharmaceutical product, according to the quality by design (QbD) definition. Therefore, the determination of analytical test conditions is extremely important and the design of experiments (DoE) becomes a very useful tool. Objective This paper used the concept of QbD to assist the development of analytical conditions for isoniazid and its respective prodrug, applying HPLC. Method HPLC analytical methodologies were developed for isoniazid and its succinylated derivative. The experimental design was carried out using three analytical parameters at three levels. Four chromatographic responses were studied. The impact of analytical parameters on chromatographic responses was assessed using a Pareto chart. Regression models were obtained using multiple regression analysis. DoE analysis was conducted using the Minitab® program and the experiments were performed sequentially, with varying factors. Results We identify three main risk parameters: mobile phase (high), flow rate (moderate), and pH of buffer (moderate). The ratio of mobile phase buffer (X2) and mobile phase pH (X3) had a major influence on the peak resolutions (Y3). The capacity factors for iso-suc (Y1) and isoniazid (Y2) peaks should be within 3–9 and 4–10, respectively. The peak resolutions between iso-suc and isoniazid (Y3) should be above two. Conclusions We designed 27 experiments, obtaining 1.0 mL/min flow rate, 95% buffer in the mobile phase, and pH 7.0 as the optimal analytical conditions. Highlights Analytical Quality by Design was used as an important tool to determine the best analytical test conditions for isoniazid and its respective prodrug - succinylated isoniazid

Developing a Validated HPLC Method for Quantification of Ceftazidime Employing Analytical Quality by Design and Monte Carlo Simulations

2021 ◽  
Author(s):  
Ranjot Kaur ◽  
Sumant Saini ◽  
Asha Patel ◽  
Teenu Sharma ◽  
Ripandeep Kaur ◽  
...  
Keyword(s):  
Monte Carlo ◽  
Monte Carlo Simulations ◽  
Flow Rate ◽  
Analytical Method ◽  
Mobile Phase ◽  
Quality By Design ◽  
Hplc Method ◽  
Superior Performance ◽  
Analytical Quality ◽  
Method Performance

Abstract Background Ceftazidime, a third-generation cephalosporin, is widely used in the treatment of lung infections, often given as “off-label” nebulization. There is need for developing a sensitive and robust analytical method to compute aerodynamic properties of ceftazidime following nebulization. Objective The current study entails development of a simple, accurate and sensitive high-performance liquid chromatography method (HPLC) for ceftazidime estimation, employing the principles of analytical quality-by-design (AQbD) and Monte Carlo simulations. Methods Selection of critical material attributes (CMAs) affecting method performance was accomplished by factor screening exercise. Subsequently, the influential CMAs, i.e., mobile phase ratio and flow rate, were systemically optimized using a face-centred cubic design for the chosen critical analytical attributes (CAAs). The factor relationship(s) between CMAs and CAAs was explored employing 3 D-response surface and 2 D-contour plots, followed by numerical as well as graphical optimization, for establishing the optimal chromatographic conditions. The obtained method operable design region was validated by Monte Carlo simulations for defect rate analysis. Results The optimized HPLC conditions for estimating ceftazidime were acetonitrile to acetic acid solution (75:25) as mobile phase at a flow rate of 0.7 mL/min, leading to Rt of 4.5 min and peak tailing ≤ 2. Validation studies, as per ICH Q2(R1) guidance’s, demonstrated high sensitivity, accuracy and efficiency of the developed analytical method with LOD of 0.075 and LOQ of 0.227 µg/mL. Application of this chromatographic method was extrapolated for determining aerodynamic performance by nebulizing ceftazidime at flow rate of 15 L/min using next-generation impactor. The study indicated superior performance, sensitivity and specificity of the developed analytical system for quantifying ceftazidime. Conclusions Application of AQbD approach, coupled with Monte Carlo simulations, aided in developing a robust HPLC method for estimation of ceftazidime per se and on various stages of impactor.

scholarly journals Development and Validation of a Ultra Flow Liquid Chromatography Method for the Assay of Boceprevir Using a Quality-by-Design Approach

2020 ◽  
Vol 11 (SPL4) ◽  
pp. 3023-3032
Author(s):  
Manish Majumder ◽  
Ramesh B ◽  
Minaketan Tripathy
Keyword(s):  
Risk Assessment ◽  
Flow Rate ◽  
Mobile Phase ◽  
Quality By Design ◽  
Quality Attributes ◽  
Assay Method ◽  
Chromatography Method ◽  
Critical Quality Attributes ◽  
Critical Method ◽  
Quality By Design Approach

Quality by design guided. The assay method of Boceprevir is developed in accordance with ICH Q8(R2) guideline with due validation. .In this process, the Target analytical profile (TAP) of the drug was set and critical method parameters (CMP) were investigated by systematic risk assessment experimentation to control critical Quality Attributes (CQA). In this, A Cause Effect Risk Assessment Matrix with Control-Noise-Experiment (CNX) is used for identifying the high-risk variables i.e Percentage of Organic Modifier (% methanol), pH of the Buffer and flow rate of the mobile phase. The surface response methodology was applied to optimize the critical method parameters (CMP) as well as Critical Quality Attributes (CQA) to find out the Design space of the method. The Optimum assay method condition was mobile phase Acetate Buffer (50mM) pH 5.4: Methanol (11:89), Flow rate: 0.9 ml/min, Lambda Max: 207. The separation was achieved in the Eclip Plus C-18 column (250 × 4.6 mm, 5μm) at ambient temperature. The retention time of Boceprevir was found to be 4.2 min. The method evaluation was performed according to the (Q2R1) ICH guideline.

scholarly journals QbD Approach for the Development and Validation of RP-UHPLC Method for Quantitation of Vildagliptin

2017 ◽  
Vol 16 (1) ◽  
pp. 107-117
Author(s):  
Sharifa Sultana ◽  
Uttom Kumar ◽  
Md Shahadat Hossain ◽  
Dilshad Noor Lira ◽  
Abu Shara Shamsur Rouf
Keyword(s):  
Flow Rate ◽  
Mobile Phase ◽  
Quality By Design ◽  
Response Surfaces ◽  
Routine Analysis ◽  
Pharmaceutical Dosage Forms ◽  
Independent Variables ◽  
Two Factors ◽  
Bulk Drug ◽  
Development And Validation

The present work describes a quality by design (QbD)-based rapid, simple, precise and robust RPUHPLC method for the routine analysis of vildagliptin in bulk drug and in pharmaceutical dosage forms. Chromatographic separation was achieved by a X-bridge C18 column with isocratic elution of mobile phase containing mixture of phosphate buffer (pH 6.8) and acetonitrile in the ratio of 67:33(v/v). The flow rate was 1.0 ml/min and the detection was done at 239 nm with photo-diode array plus (PDA+) detector. The optimization of chromatographic method was carried out by QbD approach using design of experiments (DoE). Two factors utilized for the experimental design of the method were (i) independent variables which comprise percentages of acetonitrile in mobile phase and flow rate and (ii) co-variates which include the retention time, tailing factor and theoretical plates. This design was statistically analyzed by ANOVA, normal plot of residual, box-cox plot for power transform, perturbation, counter plot and 3D response surfaces plots. This was further validated as per the requirements of ICHQ2B guidelines for linearity, LOD, LOQ, accuracy, precision, specificity and robustness. The results showed that proposed method is simple, sensitive and highly robust for routine analysis of vildagliptin.Dhaka Univ. J. Pharm. Sci. 16(1): 107-117, 2017 (June)

Degradation Profiling of Lisinopril and Hydrochlorothiazide by RP- HPLC method with QbD Approach

2021 ◽  
pp. 270-274
Author(s):  
Kalleshvar P. Jatte ◽  
R. D. Chakole ◽  
M. S. Charde
Keyword(s):  
Particle Size ◽  
Quality Control ◽  
Flow Rate ◽  
Mobile Phase ◽  
Dosage Form ◽  
Quality By Design ◽  
Hplc Method ◽  
Rp Hplc ◽  
Tablet Dosage ◽  
Gradient Mode

RP-HPLC method was developed for the estimation of Lisinopril and Hydrochlorothiazide in tablet dosage form with the help of Quality by Design (QbD) approaches. In this method concentration of each drug was obtained by using the absorptivity values calculated for drug wavelength 226.0 nm and solving the equation. The RP-HPLC method was performed C18-(100mm x 4.6 mm,)2.5 μm particle size in gradient mode, and the sample was analysed using methanol 45.0 ml and 55.0 ml (pH 3.3 0.05% OPA with TEA) as a mobile phase at a flow rate of 0.8 ml/min and detection at nm. By the retention time for Lisinopril and Hydrochlorothiazide found 3.39 and 4.59 min respectively. Validation related the method is specific, rapid, accurate, precise, reliable, and reproducible. Calibration plots by both HPLC were linear over the 5-25 and 12.5-62.5 μg/ml for Lisinopril and Hydrochlorothiazide respectively, and recoveries from tablet dosage form were between 99.02 and 100.00 %. The method can be used for routine of the quality control in pharmaceuticals. The degradation profiling of Lisinopril and Hydrochlorothiazide were also carried out.

scholarly journals ANALYTICAL QUALITY-BY-DESIGN (AQBD) APPROACH FOR THE DEVELOPMENT AND VALIDATION OF RP-HPLC METHOD FOR THE ESTIMATION OF LAMOTRIGINE IN BULK AND TABLET FORMULATION

2021 ◽  
Vol 10 (5) ◽  
pp. 3591-3596
Author(s):  
Manisha P. Puranik
Keyword(s):  
Flow Rate ◽  
Mobile Phase ◽  
High Performance ◽  
Quality By Design ◽  
Active Pharmaceutical Ingredient ◽  
Reversed Phase ◽  
Hplc Method ◽  
Analytical Technique ◽  
Rp Hplc ◽  
Ich Guideline

The current analytical exploration illustrated developing a reversed-phase high-performance liquid chromatography (RP-HPLC) technique and consequent substantiation for analyzing lamotrigine (LAM) active pharmaceutical ingredient (API) using a Quality-by-design (QbD) approach (Central Composite Design), in bulk product as well as in the tablet formulations. In this experiment, based on systematic scouting, four key components (viz., mobile phase, column, flow-rate, and wavelength) were studied by the RP-HPLC method. 13 experimental runs were done with acetonitrile (ACN) (40-60% v/v) having flow-rate in the range 0.8 mL/min to 1.2 mL/min. The proposed analytical method was thoroughly corroborated in terms of ruggedness linearity, robustness, accuracy, and precision in accordance with ICH guideline Q2A and ICH guideline Q2B. Under the optimum chromatographic environment; Intersil C8 column of 250 mm length, 4.6 mm (i.d.); 20 μL injection volume; and mobile phase ACN: Methanol (60:40 v/v), a retention time of 2.542 min was noticed at 220 nm detection wavelength. The method was found to be extremely reproducible, accurate, linear, precise, robust, and economically adequate to execute the estimation. The intended analytical technique was thoroughly assessed through statistical tools and could be an imperative concern for the habitual scrutiny of LAM in bulk products and its formulation.

scholarly journals A Critical Review on Thermo-Hydraulic Performance of Wire Screen Matrix Packed Solar Air Heaters

2021 ◽  
Author(s):  
Prashant Verma ◽  
Abhishek Saxena ◽  
L. Varshney
Keyword(s):  
Heat Transfer ◽  
Mass Flow Rate ◽  
Mass Flow ◽  
Flow Rate ◽  
Hydraulic Performance ◽  
Major Influence ◽  
Pumping Power ◽  
Bed Porosity ◽  
Wire Screen ◽  
The Impact

Solar air heaters (SAHs) have an important role in applications such as space heating and industrial drying worldwide. The packing of SAH bed not only increases the heat transfer area but also increases the pumping power losses thereby limiting the thermo-hydraulic performance. In the present study, efforts have been made for a critical assessment of the literature dealing with the impact of collector bed and operating parameters over thermal and thermo-hydraulic performance for different configurations of wire screen matrix packed SAH. The porosity of bed and mass flow rate of the air have a major influence on the thermo-hydraulic performance of wire screen matrix packed SAH. It is found that the enhancement in the volumetric heat transfer coefficient due to a decrease in bed porosity is obtained at the expense of increase in pumping power which ultimately affects the thermo-hydraulic performance of wire screen matrix packed SAH. In general it is observed that porosity is an important parameter that affects the thermo-hydraulic performance. It is seen that matrix having porosity 0.937 yields thermo-hydraulic performance of 68% at mass flow rate 0.023 kg/s where as for the same mass flow rate porosity of 0.887 results thermo-hydraulic performance of only 42%.

scholarly journals Analytical Quality by Design Approach of Reverse-Phase High-Performance Liquid Chromatography of Atorvastatin: Method Development, Optimization, Validation, and the Stability-Indicated Method

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Nabil K. Alruwaili
Keyword(s):  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
Flow Rate ◽  
Retention Time ◽  
High Performance ◽  
Method Development ◽  
Quality By Design ◽  
Water Flow Rate ◽  
Pharmacokinetic Parameters ◽  
Analytical Quality

The use of analytical quality by design (AQbD) approach in the optimization of the high-performance liquid chromatography (RP-HPLC) method is a novel tool. Three factors and three levels of Box–Behnken statistical design (BBD) were used for method optimization and analysis of atorvastatin. The mobile phase (acetonitrile: water), flow rate (Rt), and UV wavelength were used as independent variables. Their effects were observed in the area of the chromatogram (AU), retention time (Rt, min), and tailing factor (%). The optimized HPLC condition was found as acetonitrile:water (50 : 50), flow rate (0.68 ml/min), and UV wave length (235 nm). It gives the retention time of 2.43 min with the linearity range of 5–30 μg/ml with a high regression value (r2 = 0.999). The method was found to be precise and accurate with low % RSD (<5%). The refrigeration stability indicated that atorvastatin was stable. The force degradation study showed that the atorvastatin was fully unstable in UV light and stable in 0.1 M basic condition. It concluded that this QbD optimized method is suitable for quantification of the atorvastatin from the formulation as well as pharmacokinetic parameters.

ANALYTICAL QUALITY BY DESIGN APPROACH IN RP-HPLC METHOD DEVELOPMENT AND VALIDATION FOR THE ESTIMATION OF DUVELISIB

2021 ◽  
pp. 99-108
Author(s):  
SRUJANI CH ◽  
ANNAPURNA P ◽  
NATARAJ KS ◽  
KRISHNA MANJARI PAWAR A
Keyword(s):  
Flow Rate ◽  
Retention Time ◽  
Quality By Design ◽  
Hplc Method ◽  
Design Approach ◽  
Analytical Quality ◽  
Column Temperature ◽  
Rp Hplc ◽  
Validation Parameters ◽  
Quality By Design Approach

Objective: A simple, accurate, and robust RP-HPLC method was developed and validated for the estimation of Duvelisib using analytical quality by design approach. Methods: The critical method parameters (CMP) were systematically optimized using box-Behnken design (BBD). The CMP’s selected were % organic phase composition, column temperature, and flow rate. The critical quality attributes investigated were retention time and theoretical plates. Results: Chromatographic separation was accomplished on Agilent Zorbax Eclipse C18 (150×4.6 mm, 5 μm) column. The optimized and predicted data from Design Expert software consist of mobile phase 0.1 % orthophosphoric acid (46.3%): Acetonitrile (53.7%), pumped at a flow rate of 0.91 ml/min at 32.6°C gave the highest desirability function of 1. The retention time of the drug was found to be 2.85 min. The developed method was validated as per the ICH Q2 (R1) guidelines. Conclusion: Based on the analysis of variance values, the selected models were found to be significant with p<0.05. The results of the validation parameters were within the acceptable limit. The stability of the drug was examined under different stress conditions forcibly and significant degradation was found in acidic condition.

scholarly journals Application of Elements of Quality by Design to Development and Optimization of HPLC Method for Fingolimod

2021 ◽  
pp. 318-328
Author(s):  
Siddique Akber Ansari ◽  
Mrinmayee Deshpande ◽  
Jaiprakash N. Sangshetti ◽  
Sarfaraz Ahmed ◽  
Irfan Aamer Ansari
Keyword(s):  
Flow Rate ◽  
Mobile Phase ◽  
Method Development ◽  
Quality By Design ◽  
Hplc Method ◽  
Contour Plots ◽  
Target Profile ◽  
Quality By Design Approach ◽  
Actual Response

Purpose: A HPLC method for Fingolimod was developed using a Quality by Design concept. QbD has gained importance in recent times due to regulatory requirements. Actual study was started after determination of target profile and qualification of instrument. Methods: Separation was carried on a Grace C-8 column (4.6 x 250 mm, 5-μm particle size).The composition of mobile phase was methanol and 20 mM ammonium formate buffer of pH5.8 in gradient mode HPLC method development is affected by critical factors like pH, flow rate and mobile phase composition. Results: To study the effects of these three factors on USP tailing, Box Behnken optimization model was applied. Desirability of the model was set at Tailing less than 1.2.Analysis of results was done using surface diagrams. Verification of Software generated results was done by taking six replicates of the run. Thus developed and optimised method was Finally validated as per ICH guideline. Conclusion: A Quality by Design approach has been successfully utilised in method development of the Fingolimod in bulk. All key aspect of QbD were tried to be implemented in said study. Systematic approach was utilized for method development which includes beginning with determination of target profile characteristics, instrument qualification, risk assessment, design of experiment and validation. Three factors i.e. Ph, flow rate and methanol concentration were analysed for their effect on USP tailing as a responce. Interaction and quadratic effect of the factors were studied with least possible runs by using Box Behnken model. Response surface diagrams and contour plots were studied for coming to conclusion which factors are affecting response and their limits were recorded. Optimum run condition was obtained; Replicates of run having optimized condition were taken to confirm the predicted response with actual response.

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