Accreditation and Quality Assurance

Green metrics-based HPLC method for quantification of three antidiabetic drugs in tablet dosage form using Box–Behnken design

Kalpana Patel 1
, 
Babariya Raj 1
, 
Patel Ritika 1
, 
Devang Tandel 1
, 
Rajesh Parmar 1
, 
Tejal Gandhi 2
1
 
Department of Pharmaceutical Quality Assurance, Anand Pharmacy College, Anand, India | 
2
 
Department of Pharmacology, Anand Pharmacy College, Anand, India | 
Publication type: Journal Article
Publication date: 2024-11-06
scimago Q3
wos Q4
SJR: 0.274
CiteScore: 1.8
Impact factor: 0.8
ISSN: 09491775, 14320517
Abstract
This paper describes the systematic development of green and sustainable HPLC method for quantification of antidiabetic drugs teneligliptin hydrobromide hydrate, metformin hydrochloride and pioglitazone HCl in tablet formulation using Box–Behnken design. Box–Behnken design was used to know the influence of identified critical method parameters, volume of acetonitrile, flow rate and column temperature on the retention time of all three drugs and resolution between two drugs. Statistical analysis by Analysis of variance was computed to understand the potential interactions among critical method parameters. Further mathematical model was validated by using statistical and graphical optimization to define the design space. From the three parameters under investigation the study revealed that the response was more influenced by slight change in volume of acetonitrile, demanding its strict control. A mixture of KH2PO4 phosphate buffer (20 mM): acetonitrile: methanol (40:30:30%v/v) was employed as the mobile phase for chromatographic separation using octadecyl silyl column (250 × 4.6 mm, 5 µm). Detection was performed at 236 nm and 0.86 ml/min was set as the flow rate of mobile phase. The linearity was observed in the range of 12–28 µg/ml for Teneligliptin hydrobromide hydrate, 300–700 µg/ml for Metformin hydrochloride and 9–21 µg/ml for Pioglitazone hydrochloride as shown by r2 ≥ 0.99 for all three drugs. Retention time of Teneligliptin hydrobromide hydrate, Metformin hydrochloride and Pioglitazone hydrochloride was 4.09, 3.01 and 11.44 min, respectively. The % relative standard deviation for accuracy, precision and robustness were all within the specification, less than 2, which indicates that method was validated properly as per guideline. The studies successfully demonstrate the application of Box–Behnken design in the development of accurate and sensitive liquid chromatographic technique with enhanced method performance. Furthermore, greenness of the analytical method was assessed using 12 principles of green analytical chemistry by AGREE, complex GAPI and Analytical eco-scale tool, indicating that the developed method was ecofriendly.
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Oxford University Press
Stability-Indicating TLC-Densitometric and HPLC Methods for Simultaneous Determination of Teneligliptin and Pioglitazone in Pharmaceutical Dosage Forms with Eco-Friendly Assessment
Akabari A.H., Gajiwala H., Patel S.K., Surati J., Solanki D., Shah K.V., Patel T.J., Patel S.P.
Journal of Chromatographic Science scimago Q3 wos Q3 , 
2024-06-05,  citations by CoLab: 4 ,  Abstract  
Abstract The combination of teneligliptin hydrobromide hydrate and pioglitazone hydrochloride in pharmaceutical formulations has improved type 2 diabetes management. Two chromatographic methods TLC-densitometry and RP-HPLC were developed for simultaneous quantification of teneligliptin hydrobromide hydrate and pioglitazone hydrochloride in pharmaceutical formulations, ensuring accuracy and stability assessment. The TLC method uses a mobile phase of methanol, toluene, ethyl acetate and triethylamine (1:7:2:0.1, v/v/v/v) on TLC silica gel plates, scanned at 268 nm. The RP-HPLC method employs isocratic elution with acetonitrile and sodium acetate buffer (adjust pH 3.6 with glacial acetic acid, 60:40 v/v) on a shimpack C18 column (250 × 4.6 mm i.d., 5 μm), detected at 235 nm. Both methods offer high accuracy and reliability, making them valuable for pharmaceutical quality control. Additionally, an environmental impact assessment was conducted using eco-scale, Analytical Greenness Metric Approach, Green Analytical Procedure Index, and national environmental method index to evaluate solvent consumption, waste generation and energy usage. Statistical comparisons (t-tests and F-tests) validate the outcomes of both methods, ensuring their effectiveness in drug formulation analysis. These methods can enhance pharmaceutical quality control while fulfilling environmental responsibilities.
Springer Nature
Analytical quality by design (AQbD) in the ICHQ14 guidelines for analytical procedure development
Sathuluri K., Bakam R., Jain R., Dande A., Gajbhiye R., Ravichandiran V., Peraman R.
Accreditation and Quality Assurance scimago Q3 wos Q4 , 
2024-05-13,  citations by CoLab: 5 ,  Abstract  
Analytical quality by design (AQbD) is one of the risk-based approach used to develop robust analytical method in compliance with regulatory requirements. The concept of AQbD was recently established in the literature and has proven advantages in the pharma industries. Despite the differential view on AQbD, the International Council for Harmonization (ICH) has released the ICHQ14 document for analytical procedure development. Notably, the enhanced approach of the ICHQ14 document mimics AQbD workflows in analytical procedure development. Among ICHQ14 recommendations, the need for knowledge assessment, multivariate models for proven acceptable range (PARs) as method operable region, sample suitability assessment in robustness, and real-time release testing with product critical quality attribute specifications  as the challenging components for pharmaceutical industries. In addition, the integration of ICHQ14 with other ICH documents like ICH Q6A/6B, ICHQ8, ICHQ9, ICHQ10, ICHQ11, and ICHQ12 are well defined in the document. Thus, the revised ICHQ2 (R2) guideline has defined the validation procedure with integration to ICHQ14 documents.
Springer Nature
Diabetes and infection: review of the epidemiology, mechanisms and principles of treatment
Holt R.I., Cockram C.S., Ma R.C., Luk A.O.
Diabetologia scimago Q1 wos Q1 , 
2024-02-20,  citations by CoLab: 30 ,  Abstract  
AbstractAn association between diabetes and infection has been recognised for many years, with infection being an important cause of death and morbidity in people with diabetes. The COVID-19 pandemic has re-kindled an interest in the complex relationship between diabetes and infection. Some infections occur almost exclusively in people with diabetes, often with high mortality rates without early diagnosis and treatment. However, more commonly, diabetes is a complicating factor in many infections. A reciprocal relationship occurs whereby certain infections and their treatments may also increase the risk of diabetes. People with diabetes have a 1.5- to 4-fold increased risk of infection. The risks are the most pronounced for kidney infection, osteomyelitis and foot infection, but are also increased for pneumonia, influenza, tuberculosis, skin infection and general sepsis. Outcomes from infection are worse in people with diabetes, with the most notable example being a twofold higher rate of death from COVID-19. Hyperglycaemia has deleterious effects on the immune response. Vascular insufficiency and neuropathy, together with altered skin, mucosal and gut microbial colonisation, contribute to the increased risk of infection. Vaccination is important in people with diabetes although the efficacy of certain immunisations may be compromised, particularly in the presence of hyperglycaemia. The principles of treatment largely follow those of the general population with certain notable exceptions. Graphical Abstract
Akademiai Kiado
Methods for experimental design, central composite design and the Box–Behnken design, to optimise operational parameters: A review
Szpisják-Gulyás N., Al-Tayawi A.N., Horváth Z.H., László Z., Kertész S., Hodúr C.
Acta Alimentaria scimago Q3 wos Q4 , 
2023-12-04,  citations by CoLab: 43 ,  Abstract  
AbstractIn recent years response surface analysis has been increasingly used to optimise membrane separation. It has many advantages, such as reducing the number of experiments to be performed, which requires lower energy consumption and significantly less laboratory work. For more accurate data analysis and forecasting, mathematical models are used that analyse the relevance of the factors examined and the interaction effects between the factors. In this research, two experimental designs that use response surface methodology are presented, namely, the central composite design and the Box–Behnken design. After the general characterisation of the experimental designs, their application in membrane technology is presented.
Akademiai Kiado
Box‒Behnken design-assisted development of an eco-friendly thin-layer chromatography‒densitometry method for the quantification of amlodipine besylate, metoprolol succinate, and telmisartan in synthetic mixture using AGREE tool
Patel K., Macwan P., Prajapati A., Patel H., Parmar R.
Journal of Planar Chromatography - Modern TLC scimago Q3 wos Q4 , 
2023-10-26,  citations by CoLab: 1 ,  Abstract  
This study describes the systematic development of a high-performance thin-layer chromatography (HPTLC) method for the quantification of amlodipine besylate (AML), metoprolol succinate (MET), and telmisartan (TEL) in synthetic mixture within the quality by design framework. A mixture of toluene‒methanol‒isopropanol‒triethylamine (6:0.8:2:0.2, V/V) was used as the mobile phase for chromatographic separation on aluminum-backed silica gel 60 F254 plates with densitometric scanning at 233 nm. The effects of identified critical method parameters, volume of methanol, chamber saturation duration, and solvent front on the RF value of all three drugs and resolution between two drugs were investigated using Box‒Behnken experimental design. To understand potential interactions among critical method parameters, statistical modelization was used, followed by response surface analysis. By using numerical and graphical optimization to define the design space, the search for the best solution was carried out. The RF values discovered after optimization for AML, MET, and TEL were 0.25, 0.39, and 0.48, respectively. The calibration plots’ data from the linear regression analysis indicated a regression coefficient more than 0.99 for a concentration range of 500–2500 ng/band for AML, 400–2000 ng/band for MET, and 100–500 ng/band for TEL. The optimized HPTLC method was validated according to the International Council for Harmonisation (ICH) guideline Q2 (R1). The %RSD for accuracy, precision, and robustness were all within the acceptable range, less than 2. Additionally, the AGREE greenness assessment tool was used to analyze the greenness profile of the developed method, the score of 0.79 proved that the technique is environmentally friendly and can be regularly used for the analysis of all three drugs in combination. The investigations effectively show the applicability of the quality by design (QbD) strategy in the development of the highly sensitive HPTLC method with improved method performance.
Springer Nature
Box–Behnken design-assisted optimization of RP-HPLC method for the estimation of evogliptin tartrate by analytical quality by design
Patel K., Shah U.A., Patel C.N.
Future Journal of Pharmaceutical Sciences wos Q2 Open Access , 
2023-07-19,  citations by CoLab: 7 ,  PDF,  Abstract  
Abstract Background A quality by design approach can potentially lead to a more robust/rugged method development due to emphasis on the risk assessment and management. By carefully understanding the step-by-step procedure for analytical QbD-based optimization parameters, such as analytical target profile and critical quality attributes (CQAs), was assessed. The present study describes the simple, rapid, sensitive and cost-effective RP-HPLC method development and validation for the estimation of evogliptin tartrate in pharmaceutical dosage form. Results The factor screening studies were performed using Box–Behnken design by three key components of the RP-HPLC method (mobile phase, pH and flow rate). The chromatographic conditions were optimized with the Design Expert software trial version 13.0. The optimal chromatographic separation was achieved having water C18 column (250 mm × 4.6 mm, 5 μ) and using mobile phase as a methanol and phosphate buffer (pH 4.5) 60:40% v/v with a flow rate 1.0 ml/min and UV detection at 267 nm. The Box–Behnken experimental design describes the interrelationship of mobile phase, pH and flow rate at three different levels, and responses of retention time and tailing factor were observed with response surface plot and statistical data. The developed method was validated as per recommended ICH guidelines which revealed the high degree of linear, precise, accurate, sensitive and robust method over the existing RP-HPLC method for evogliptin tartrate. Conclusion The developed QbD-based method helped in generating a design space and operating space with knowledge of all method performance characteristics, and RP-HPLC method takes less time and can be used in the industry for routine quality control of bulk and marketed formulation of evogliptin tartrate.
A Box-Behnken design optimization based ecofriendly RP-HPLC method For Estimation of sofosbuvir And velpatasvir - Application to stability indicating assay
Bairam R., Tatapudi H.K., Gajji N., Tammineni N., Cheepurupalli P.
2023-06-28,  citations by CoLab: 1 ,  Abstract  
Abstract In this study, a novel, cost effective, accurate, and ecofriendly stability-indicating RP-HPLC technique was developed and validated for the simultaneous measurement of sofosbuvir (SOF) and velpatasvir (VEL) in tablet dosage form. Box-Behnken design was used for multivariate optimization of the experimental parameters of RP-HPLC. The molarity of heptane sulfonic acid sodium salt (HSA), volume of ethanol, and volume of acetonitrile were used to develop mathematical models and study the effects of these factors on various responses. Heptane sulfonic acid sodium (1mM) : acetonitrile : ethanol (80 : 11 : 9 v/v) as the mobile phase, made up the optimal and expected condition. The SOF and VEL retention times were found to be 5.505 and 3.472 minutes, respectively. System suitability, specificity, accuracy, linearity, precision, and solution stability were all considered in the method's validation. For SOF and VEL, linearity was shown across the concentration range of 20–100 µg/ml and 5–25 µg/ml, respectively with correlation coefficient (R2) > 0.999. Studies on forced degradation under acid, basic, oxidative, photolytic, and thermal conditions revealed the drug's well-resolved peak and the degradation products' peaks as well. For the simultaneous determination of sofosbuvir and velpatasvir in conventional laboratory analysis, this newly suggested approach is one that is quick, reliable, and cost-effective. Furthermore, the greenness was analyzed utilizing four cutting-edge metrics, including GAPI, AES, AMGS, and AGREE, and the greenest findings were determined.
A Simple, Precise, and Sensitive RP-HPLC Method for Quantification of Teneligliptin Hydrobromide and Metformin Hydrochloride: Development and Validation
M. Patel M., Patel D., Shah U., M. Kachhiya H.
Research Journal of Pharmacy and Technology scimago Q2 , 
2023-02-28,  citations by CoLab: 6 ,  Abstract  
Simple, rapid, sensitive, robust, and validated reverse phase- high-performance liquid chromatography RP_(HPLC) was developed for the quantification of anti-diabetic drugs Teneligliptin hydrobromide (TH) and Metformin hydrochloride (MH) in bulk and in formulation. The RP-HPLC method was developed using an HPLC system with a PDA detector. A simple, accurate and cost-effective gradient approach is used by using C18 Inertsil ODS (150×4.6)mm, 5µ. A method was developed and validated as per ICH Q2 (R1) guideline. The efficient separation of both drugs was achieved using an optimised solvent mixture of Buffer: ACN (85:15% v/v) and Methanol: ACN (50:50% v/v) used as a gradient mobile phase, during this experiments flow rate was maintained 0.8 ml/min and at the end the detection of peak carried out by PDA detector at wavelength 249nm. The method has been validated for TH and MH for a range of 16-64μg/ml and 400 - 1600μg/ml with regression coefficient (r2) was 1 and 0.9979 respectively. The optimal approach has been validated in accordance with ICH guideline Q2(R1). The results demonstrated that the method’s accuracy (99.89–100.34 percent w/w and 99.91–100.01 percent w / w TH and MH, respectively) and method is precise as percentage of relative standard deviation <2.0. The proposed LC method used as qualitative as well as quantitative applications for simultaneous quantification of Teneligliptin hydrobromide and Metformin hydrochloride in bulk and tablet dosage form and also sufficient to apply regulatory purpose.
Springer Nature
Application of Box-Behnken experimental design and response surface methodology for selecting the optimum RP-HPLC conditions for the simultaneous determination of methocarbamol, indomethacin and betamethasone in their pharmaceutical dosage form
Elkady E.F., Fouad M.A., Mozayad A.N.
BMC Chemistry scimago Q2 wos Q2 Open Access , 
2022-12-12,  citations by CoLab: 26 ,  PDF,  Abstract  
AbstractAn isocratic RP-HPLC method has been developed for the separation and determination of methocarbamol (MTL), indomethacin (IND), and betamethasone (BET) in combined dosage form using an Inertsil ODS-3v C18 (250 × 4.6 mm, 5 μm) column with UV- detection at 235 nm. Experimental design using Box-Behnken design (BBD) was applied to study the response surface during method optimization and to achieve a good separation with a minimum number of experimental runs. The three independent parameters were pH of buffer, % of acetonitrile and flow rate of the mobile phase while the peak resolution of IND from MTL and the peak resolution of BET from IND (R2) were taken as responses to obtain mathematical models. The composite desirability was employed to optimize a set of responses overall (peak resolutions). The predicted optimum assay conditions include a mobile phase composition of acetonitrile and phosphate buffer (pH 5.95) in a ratio of 79:21, v/v, pumped at a flow rate of 1.4 mL min−1. With this ideal condition, the optimized method was able to achieve baseline separation of the three drugs with good resolution and a total run time of less than 7 min. The linearity of MTL, IND, and BET was determined in the concentration ranges of 5–600 µg mL− 1, 5–300 µg mL− 1, and 5–300 µg mL− 1 and the regression coefficients were 0.9994, 0.9998, and 0.9998, respectively. The average percent recoveries for the accuracy were determined to be 100.41 ± 0.60%, 100.86 ± 0.86%, and 100.99 ± 0.65% for MTL, IND, and BET, respectively. The R.S.D.% of the intra-day precision was found to be less than 1%, while the R.S.D.% of the inter-day precision was found to be less than 2%. The RP-HPLC method was fully validated with regard to linearity, accuracy, precision, specificity, and robustness as per ICH recommendations. The proposed method has various applications in quality control and routine analysis of the investigated drugs in their pharmaceutical dosage forms and laboratory-prepared mixtures with the goal of reducing laboratory waste, analysis time, and effort.
Wiley
Stability‐indicating HPLC method development and validation for simultaneous estimation of metformin, dapagliflozin, and saxagliptin in bulk drug and pharmaceutical dosage form
Vankalapati K.R., Alegete P., Boodida S.
Biomedical Chromatography scimago Q3 wos Q3 , 
2022-04-29,  citations by CoLab: 9 ,  Abstract  
A simple, precise, and rapid stability-indicating reversed-phase-HPLC method was developed and validated for the estimation of metformin (MET), dapagliflozin (DAP), and saxagliptin (SAX) combination in bulk and tablet dosage forms. The proposed method uses a Kromasil C18 column (150 × 4.6 mm, 5 μm) with column oven temperature of 30°C and mobile phase containing a mixture of 60% phosphate buffer (pH = 3) and 40% acetonitrile. The flow rate was set at 1.0 mL/min, and the injection volume was 10 μL. The detection was carried out at 230 nm using a photodiode array detector, and the total run time was 4 min. The proposed method was validated according to International Council for Harmonisation (ICH) guidelines for specificity, linearity, precision, accuracy, robustness, and solution stability. The method is linear over the range of 125-750 μg/mL for MET, 1.25-7.5 μg/mL for DAP, and 0.625-3.75 μg/mL for SAX. The observed correlation coefficients (R2 ) for MET, DAP, and SAX are >0.999. The proposed method is precise, and the percentage relative standard deviation was found to be between 0.4 and 0.8. The observed percentage recoveries were between 98.51 and 100.80 for all three compounds. The product was subjected to stress conditions of acid, base, oxidative, thermal, and photolytic degradation. The product was found to degrade significantly in oxidative, acid, and base hydrolysis degradation conditions, and the degradation products were well determined from the active peaks, thus proving the stability-indicating power of the method. The developed and validated stability-indicating reversed-phase-HPLC method was appropriate for quantitative determination of these drugs in pharmaceutical preparations and also for quality control in bulk manufacturing.
MDPI
Development and Validation of Rapid RP-HPLC and Green Second-Derivative UV Spectroscopic Methods for Simultaneous Quantification of Metformin and Remogliflozin in Formulation Using Experimental Design
Attimarad M., Elgorashe R.E., Subramaniam R., Islam M.M., Venugopala K.N., Nagaraja S., Balgoname A.A.
Separations scimago Q3 wos Q3 Open Access , 
2020-10-29,  citations by CoLab: 24 ,  PDF,  Abstract  
Recently, a new formulation containing metformin HCl (MFH) and remogliflozin etabonate (RGE) has been approved for the management of diabetes mellitus. However, only one analytical method has been reported for the simultaneous determination of both the analytes. Therefore, the current study was designed to develop simple UV derivative spectroscopic and rapid RP-HPLC methods for simultaneous determination of MFH and RGE. The chromatographic separation of MFH and RGE was performed using a monolithic C18 column with an optimized chromatographic conditions carried out by full factorial Box–Behnken design model. The spectroscopic technique was based on the determination of peak amplitude of second-order derivative UV spectra at zero crossings. Further, both the methods were validated and compared statistically using Student’s-t-test and F-test, and employed for the concurrent estimation of MFH and RGE in laboratory mixed solutions and formulations. Perturbation plots and response surface models showed the effect of chromatographic parameters and the final chromatographic condition was selected from 47 solutions suggested by the desirability function. Further, UV spectroscopic and HPLC procedures showed good linearity in the range of 1–24 µg/mL and 2–150 µg/mL for RGE and 2–30 µg/mL and 5–200 µg/mL for MFH, respectively. The average percent assay was found to be 99.51% and 99.80% for MFH and 99.60% and 100.07% for RGE by spectroscopic and HPLC methods, respectively. The proposed methods were simple, accurate, precise, and rapid. Therefore, they can be used for regular quality control of MFH and RGE formulations and dissolution studies as well.
Wiley
A multivariate quantification of Box‐Behnken design assisted method development and validation of dextromethorphan hydrobromide and desloratadine simultaneously by reverse‐phase HPLC in in‐house syrup formulation
Alam M.I., Siddiqui A.U., Khanam N., Kamaruddin S.J.
Journal of Separation Science scimago Q2 wos Q2 , 
2020-08-09,  citations by CoLab: 6 ,  Abstract  
An innovative high-performance liquid chromatography assay method was developed and validated for quantification of dextromethorphan hydrobromide and desloratadine simultaneously in monophasic liquid formulation by preparing syrup containing 30 mg/5 mL of dextromethorphan hydrobromide and 1.2 mg/mL of desloratadine. The chromatographic severance was executed by gradient solution A and B. The composition of buffer solution A contained 0.05 M monobasic potassium, then 1 mL triethylamine was added to it and the pH was adjusted to 2.3 with orthophosphoric acid. Methanol was used as solution B. The gradient elution was executed with Kromasil C8 (250 mm × 4.6 mm) column having 1.5 mL/min flow rate and 20 µL injection volume with UV-estimation at 254 nm for dextromethorphan hydrobromide and DES. The present research was planned according to Box-Behnken design by utilizing design expert software, using four factors such as column temperature (A), flow rate (B), mobile phase-organic phase (C), and pH (D); correspondingly the selected response variables were resolution between A and B, that is, desloratadine and methyl paraben (Y1), tailing of dextromethorphan hydrobromide (Y2), and tailing of desloratadine (Y3). The parameters such as system suitability, linearity, accuracy, precision, robustness, limit of detection, limit of quantitation, and ruggedness were analyzed to validate the developed method in accordance with current regulatory guidelines.
Development and Validation of an Analytical Method for the Estimation of Metformin and Teneligliptin in its Bulk and Tablet Dosage Form by using RP-HPLC
Bichala P.K., Kumar K.J., Suthakaran R., Shankar C.
Asian Journal of Pharmaceutical Analysis , 
2020-06-03,  citations by CoLab: 9 , 
Akademiai Kiado
Densitometric simultaneous estimation of combination of empagliflozin, linagliptin and metformin hydrochloride used in the treatment of type 2 diabetes mellitus
Patel I.M., Chhalotiya U.K., Jani H.D., Kansara D., Shah D.A.
Journal of Planar Chromatography - Modern TLC scimago Q3 wos Q4 , 
2020-04-01,  citations by CoLab: 17 ,  Abstract  
A sensitive, accurate, precise, and robust high-performance thin-layer chromatography (HPTLC) method has been developed for the simultaneous quantification of empagliflozin, linagliptin, and metformin HCl in bulk and synthetic mixture. The method applied HPTLC aluminum plates pre-coated with silica gel 60 F254 as the stationary phase along with n-butanol:water:glacial acetic acid (6:3:1, v/v) as the mobile phase. The Rf values of empagliflozin, linagliptin, and metformin HCl were found to be 0.73, 0.52, and 0.33, respectively. Densitometric analysis was carried out in the absorbance mode at 223 nm. The method was obtained linear in the range of 0.1–0.7 μg/band for empagliflozin, 0.05–0.35 μg/band for linagliptin, and 10–70 μg/band for metformin HCl, respectively. From synthetic mixture, the percentage (%) amounts of all three drugs were found to be more than 98% by the proposed HPTLC method. The method was validated as per the International Conference on Harmonisation (ICH) guideline Q2(R1).
Development and Validation of a Stability-indicating RP-HPLC Method for Estimation of Metformin and Rosuvastatin along with Impurities from a Combined Oral Solid Dosage Form
Sangeetha D., Vadlamudi M.K.
2019-09-18,  citations by CoLab: 4 , 

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