Whiteness, redness, blueness and greenness profile assessment and design of experiments approach to microwave-aided sensitive and green spectrofluorophotometric determination of baclofen.

As a gamma amino butyric acid-ergic agonist, Baclofen is often prescribed to adults and children for the treatment of severe spasticity that originates in the brain or spinal cord. Even after reviewing the literature extensively, no one has documented a method for estimating baclofen using microwave-assisted stability-indicating spectrofluorimetric techniques, despite the abundance of options for baclofen stability, assay, and bioanalysis. Organic solvents, which are typically necessary for current procedures but may be costly and toxic, have a severe effect on aquatic life and the environment. Using green solvents and 4-chloro-7-nitrobezofuran as a fluorescent probe, this work conducted a stability-indicating spectrofluorimetric estimate of baclofen. Through the use of a design-of-experiments technique, a reliable microwave-aided spectrofluorimetric method was developed, with little solvent consumption and time for sample analysis. Prior to conducting response surface analysis and optimizing important variables and responses, a fractional factorial design was used to screen method variables and responses. A central composite design was then employed for these purposes. This flexible spectrofluorimetric technique was used to assess baclofen concentrations in forced degraded samples and marketed formulations. For baclofen determination, the suggested spectrofluorimetric approach was found to be green, quick, easy to use, economical, and user-friendly.

Selective detection of azelnidipine in pharmaceuticals via carbon dot mediated spectrofluorimetric method: A green approach.

A spectrofluorimetric method using fluorescent carbon dots (CDs) was developed for the selective detection of azelnidipine (AZEL) pharmaceutical in the presence of other drugs. In this study, N-doped CDs (N-CDs) were synthesized through a single-step hydrothermal process, using citric acid and urea as precursor materials. The prepared N-CDs showed a highly intense blue fluorescence emission at 447 nm, with a photoluminescence quantum yield of ~21.15% and a fluorescence lifetime of 0.47 ns. The N-CDs showed selective fluorescence quenching in the presence of all three antihypertensive drugs, which was used as a successful detection platform for the analysis of AZEL. The photophysical properties, UV-vis light absorbance, fluorescence emission, and lifetime measurements support the interaction between N-CDs and AZEL, leading to fluorescence quenching of N-CDs as a result of ground-state complex formation followed by a static fluorescence quenching phenomenon. The detection platform showed linearity in the range 10-200 µg/ml (R2 = 0.9837). The developed method was effectively utilized for the quantitative analysis of AZEL in commercially available pharmaceutical tablets, yielding results that closely align with those obtained from the standard method (UV spectroscopy). With a score of 0.76 on the 'Analytical GREEnness (AGREE)' scale, the developed analytical method, incorporating 12 distinct green analytical chemistry components, stands out as an important technique for estimating AZEL.

White analytical chemistry-driven stability-indicating concomitant chromatographic estimation of thiocolchicoside and aceclofenac using response surface analysis and red, green, and blue model.

White analytical chemistry is a novel concept for the assessment of analytical methods on basis of its validation efficiency, greenness power, and economical efficiency. White analytical chemistry-driven stability indicating chromatographic method has been developed for the concomitant analysis of thiocolchicoside and aceclofenac. The proposed chromatographic method has been developed using a safe and environmental-friendly organic solvents for the concomitant stability study of thiocolchicoside and aceclofenac. The analytical risk assessment was carried out for the identification of high-risk analytical risk factors and analytical method performance attributes. The mixture design was applied for the design of experiments-based response surface modeling of high-risk analytical risk factors and analytical method performance attributes. The degradation products were isolated and characterized using infrared, nuclear magnetic resonance, and mass spectral data. The proposed method was compared for its validation efficiency, greenness power, and cost-efficiency with published chromatographic methods using the red, green, and blue models. The white score of the proposed and reported method was calculated by averaging the red, green, and blue scores of the methods. The proposed method was found to be robust, green, and economical for the concomitant stability study of thiocolchicoside and aceclofenac.

Green analytical chemistry-driven response surface modeling to stability-indicating chromatographic method for estimation of cilnidipine and application of high-performance thin-layer chromatography-mass spectrometry for characterization of degradation products.

Cilnidipine is a calcium channel blocker that is used to treat cardiac diseases such as angina and high blood pressure. Several column and planar chromatographic methods for estimating cilnidipine in pharmaceutical dosage forms have been documented. However, these method developments have been carried out employing organic solvents such as acetonitrile, methanol, toluene, chloroform, and others as mobile phase components or as sample pretreatment diluents. These organic solvents are neurotoxic and teratogenic to humans and aquatic animals, according to International Council for Harmonization Q3C (R8) recommendations. According to the green analytical chemistry approach, such organic solvents should be reduced or removed during the development of chromatographic methods for environmental protection and the safety of human and aquatic animal life. As a result, the stability-indicating chromatographic estimation of cilnidipine was performed utilizing less toxic organic solvents. To prevent organic solvent waste during method development, mobile-phase optimization was performed using the design of experiment-based response surface modeling. Cilnidipine has been subjected to hydrolysis, oxidation, photolysis, and dry-heat decomposition to determine its stability. The greenness profiles of the suggested and published chromatographic methods were examined using the national environment method index, analytical greenness calculator, green analytical procedure index software, and eco-scale assessment tool.

Discovery of a potent G-protein-coupled receptor 119 agonist for the treatment of type 2 diabetes.

The ever-growing prevalence of Type-2 diabetes in the world has an urgent need for multiple orally effective agents that can regulate glucose homeostasis. G-Protein coupled receptor 119 (GPR 119) agonists have demonstrated the glucose-dependent insulin secretion and showed beneficial effects on glycemic control in humans and/or relevant animal models. Herein, we describe our efforts towards identification of a potent and oral GPR 119 agonist 13c (ZY-G19), which showed in vitro potency in the cell-based assay and in vivo efficacy without exerting any significant signs of toxicity in relevant animal models.

Anticancer, antimicrobial activities of quinoline based hydrazone analogues: Synthesis, characterization and molecular docking.

Based on the biologically active heterocycle quinoline, a series (18a-p) of quinoline hydrazone analogues were prepared, starting from 6-bromo/6-chloro-2-methyl-quinolin-4-yl-hydrazines. For all the newly synthesized compounds cytotoxic activities were carried out at the National Cancer Institute (NCI), USA, against full NCI 60 human cancer cell lines. Amongst all the tested compounds, nine compounds (18b, 18d, 18e, 18f, 18g, 18h, 18i, 18j, 18l) exhibited important anti-proliferative activity at 10 µM concentration and were further screened at 10-fold dilutions of five different concentrations (0.01, 0.1, 1, 10 and 100 µM) with GI50 values ranging from 0.33 to 4.87 µM and LC50 values ranging from 4.67 µM to >100j µM. Further, the mean values of GI50, TGI and LC50 of the most potent compound 18j were compared with the clinically used anticancer agents bendamustine and chlorambucil, revealed that the quinolyl hydrazones holds promise as a potential anticancer agents. Further all the newly prepared compounds were screened for their antimicrobial activity. All the quinolyl hydrazones displayed good to excellent antimicrobial activity with MIC values ranging from 6.25 to 100 µg/mL against the tested pathogenic strains. Molecular docking of the synthesized compounds into the active binding site of human DNA topoisomerase I (htopoI) was carried out to predict the binding mode to the DNA topoisomerase I inhibitors. Hopefully in future, compounds based on quinoline core could be used as a lead compounds for designing new anticancer agents.

Nocturia - Symptom or a Disease?

Waking at night to void is known as nocturia and it is a common condition experienced by both men and women with profound impact on patient's health, quality of life, and economic condition. It is often perceived as a symptom of an organic disease, but the pathophysiology of nocturia is now well-understood, and it is considered as a disease itself. It is classified based on four different pathophysiologic mechanisms (24-hour polyuria, nocturnal polyuria, reduced bladder capacity, and sleep disorders). The association of nocturia with impaired quality of life, cardiovascular morbidity and all-cause mortality is well established. Various pharmacological agents are available, of which desmopressin is considered safe and effective in both short- and long-term studies for the treatment of nocturia in men and women, including the elderly. Combining desmopressin with other agents provides an effective treatment option for nocturia in patients with lower urinary tract symptoms, benign prostatic hypertrophy or overactive bladder syndrome. This review covers the various aspects of pathophysiology and impact of nocturia, as well as the treatment of nocturia. We present the novel concept of a "nocturia clinic", which is a comprehensive diagnostic and management center for patients with nocturia. This set-up may help bring about a positive change in the underreported and undertreated status of nocturia, and bring relief to sufferers of nocturia. Therefore nocturia though perceived as a symptom of many disorders; it itself has a defined pathophysiology and needs treatment.

Effect of roughage on rumen microbiota composition in the efficient feed converter and sturdy Indian Jaffrabadi buffalo (Bubalus bubalis).

BACKGROUND: The rumen microbiota functions as an effective system for conversion of dietary feed to microbial proteins and volatile fatty acids. In the present study, metagenomic approach was applied to elucidate the buffalo rumen microbiome of Jaffrabadi buffalo adapted to varied dietary treatments with the hypothesis that the microbial diversity and subsequent in the functional capacity will alter with diet change and enhance our knowledge of effect of microbe on host physiology. Eight adult animals were gradually adapted to an increasing roughage diet (4 animals each with green and dry roughage) containing 50:50 (J1), 75:25 (J2) and 100:0 (J3) roughage to concentrate proportion for 6 weeks. Metagenomic sequences of solid (fiber adherent microbiota) and liquid (fiber free microbiota) fractions obtained using Ion Torrent PGM platform were analyzed using MG-RAST server and CAZymes approach. RESULTS: Taxonomic analysis revealed that Bacteroidetes was the most abundant phylum followed by Firmicutes, Fibrobacter and Proteobacteria. Functional analysis revealed protein (25-30 %) and carbohydrate (15-20 %) metabolism as the dominant categories. Principal component analysis demonstrated that roughage proportion, fraction of rumen and type of forage affected rumen microbiome at taxonomic as well as functional level. Rumen metabolite study revealed that rumen fluid nitrogen content reduced in high roughage diet fed animals and pathway analysis showed reduction in the genes coding enzymes involved in methanogenesis pathway. CAZyme annotation revealed the abundance of genes encoding glycoside hydrolases (GH), with the GH3 family most abundant followed by GH2 and GH13 in all samples. CONCLUSIONS: Results reveals that high roughage diet feed improved microbial protein synthesis and reduces methane emission. CAZyme analysis indicated the importance of microbiome in feed component digestion for fulfilling energy requirements of the host. The findings help determine the role of rumen microbes in plant polysaccharide breakdown and in developing strategies to maximize productivity in ruminants.

Design, synthesis and biological evaluation of novel aminomethyl-piperidones based DPP-IV inhibitors.

A series of novel aminomethyl-piperidones were designed and evaluated as potential DPP-IV inhibitors. Optimized analogue 12v ((4S,5S)-5-(aminomethyl)-1-(2-(benzo[d][1,3]dioxol-5-yl)ethyl)-4-(2,5-difluorophenyl)piperidin-2-one) showed excellent in vitro potency and selectivity for DPP-IV over other serine proteases. The lead compound 12v showed potent and long acting antihyperglycemic effects (in vivo), along with improved pharmacokinetic profile.

Simultaneous Chromatographic Estimation of Vildagliptin and Dapagliflozin Using Hybrid Principles of White Analytical Chemistry and Analytical Quality by Design.

BACKGROUND: The fixed-dose combination of vildagliptin (VDG) and dapagliflozin (DGZ) is used in the treatment of type 2 diabetes mellitus. According to the literature survey, RP-HPLC and HPTLC methods have been reported for routine analysis of VDG and DGZ. These chromatographic methods have been developed using potentially neurotoxic and teratogenic solvents, which are unsafe for human and aquatic animal life and hazardous to the environment. These types of organic solvents shall be replaced or reduced during chromatographic analysis of drugs for the safety of human and aquatic animal life and the protection of the environment. The novel white analytical chemistry (WAC) approach has been introduced, which emphasizes robust, green, user-friendly, economical, and rapid analysis of drug samples. OBJECTIVE: Hence, the WAC-based RP-HPLC method has been developed for the estimation of VDG and DGZ using lower toxic and economical solvents. METHOD: The development of the RP-HPLC method includes the implementation of the analytical quality by design approach using principles of design of experiments to reduce organic waste generation and regulatory compliance of analytical method. The central composite design was applied for response surface modeling (RSM) and optimization of the RP-HPLC method. The method validation was carried out according to ICH Q2 (R1) guidelines. RESULTS: The fixed-dose combinations of VDG and DGZ were assayed, and results were found in compliance with their labeled claim. The published and proposed RP-HPLC methods were assessed for chromatographic analysis of VDG and DGZ using the Red-Green-Blue (RGB) model, AGREE calculator, Eco-Scale Assessment tool, GAPI software, and NEMI standards. CONCLUSIONS: The proposed method was found to be robust, green, economical, and user-friendly for chromatographic analysis of VDG and DGZ. The proposed method can be an economical and eco-friendly analytical tool in the pharmaceutical industry for quality control and routine analysis of fixed-dose combinations of VDG and DGZ. HIGHLIGHTS: Hybrid principles of WAC and analytical quality by design to RP-HPLC method for simultaneous estimation of VDG and DGZ in their fixed-dose combinations.

Integrated approach of white analytical chemistry and design of experiments to microwave-assisted sensitive and eco-friendly spectrofluorimetric estimation of mirabegron using 4-chloro-7-nitrobezofuran as biosensing fluorescent probe.

The USFDA recently approved mirabegron, a novel once-daily ß-3 adrenoceptor agonist for oral administration, as a transformative treatment for overactive bladder. Despite the existence of numerous analytical methods for the assay and bioanalysis of mirabegron, it's perplexing that none have explored the domain of microwave-assisted sensitive spectrofluorimetric method for mirabegron estimation, even after extensive literature review. Adding to the enigma is the insistence of current analytical methods on using expensive and harmful organic solvents, posing a threat to marine life and the broader environment. Recently, the white analytical chemistry approach has been introduced to develop analytical methods that are cost-effective, environmentally friendly, and user-friendly. Consequently, a white analytical chemistry-based, sensitive, and eco-friendly spectrofluorimetric estimation of mirabegron has been initiated, using 4-Chloro-7-nitrobenzofurazan as a fluorescent biosensing probe. The development of this robust method involved a series of experiments designed to minimize solvent and time wastage. Through a combination of fractional factorial and Box-Behnken designs, researchers identified the critical variables and optimized the method to perfection. This method was validated according to the stringent ICH Q2 (R2) and USFDA guidelines, ensuring its reliability and accuracy. Once approved, this sensitive spectrofluorimetric method was tested, accurately estimating mirabegron levels in commercial formulations and rat plasma samples. To further enrich the study, a comprehensive evaluation of existing analytical methods was conducted alongside the proposed spectrofluorimetric method, using advanced tools like the AGREE calculator, GAPI software, and RGB model to assess their eco-friendliness and effectiveness in mirabegron estimation.

In-vivo pharmacokinetic study of ibrutinib-loaded nanostructured lipid carriers in rat plasma by sensitive spectrofluorimetric method using harmonized approach of quality by design and white analytical chemistry.

Ibrutinib, an antineoplastic agent tackling chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenstrom's Macroglobulinemia, falls under the category of BCS class II drugs, characterized by a puzzling combination of low solubility and high permeability. Its oral bioavailability remains a perplexing challenge, merely reaching 2.9 % due to formidable first-pass metabolism hurdles. In a bid to surmount this obstacle, researchers embarked on a journey to develop ibrutinib-loaded NLCs (Nanostructured Lipid Carriers) using a methodology steeped in complexity: a Design of Experiments (DoE)-based hot melted ultrasonication approach. Despite a plethora of methods for analyzing ibrutinib in various matrices, the absence of a spectrofluorimetric method for assessing it in rat plasma added to the enigma. Thus emerged a spectrofluorimetric method, embodying principles of white analytical chemistry and analytical quality by design, employing a Placket-Burman design for initial method exploration and a central composite design for subsequent refinement. This method underwent rigorous validation in accordance with ICH guidelines, paving the way for its application in scrutinizing the in-vivo pharmacokinetics of ibrutinib-loaded NLCs, juxtaposed against commercially available formulations. Surprisingly, the optimized NLCs exhibited a striking 1.82-fold boost in oral bioavailability, shedding light on their potential efficacy. The environmental impact of this method was scrutinized using analytical greenness tools, affirming its eco-friendly attributes. In essence, the culmination of these efforts has not only propelled advancements in drug bioavailability but also heralded the dawn of a streamlined and environmentally conscious analytical paradigm.

Hydrochloride salt co-crystals: preparation, characterization and physicochemical studies.

Co-crystallization approach for modification of physicochemical properties of hydrochloride salt is presented. The objective of this investigation was to study the effect of co-crystallization with different co-crystal formers on physicochemical properties of fluoxetine hydrochloride (FH). FH was screened for co-crystallization with a series of carboxylic acid co-formers by slow evaporation method. Photomicrographs and melting points of crystalline phases were determined. The co-crystals were characterized by FTIR, DSC and PXRD methods. Solubility of co-crystals was determined in water and buffer solutions. Powder and intrinsic dissolution profiles were assessed for co-crystals. Physical mixtures of drug and co-formers were used for comparisons at characterizations and physicochemical properties evaluation stages. Four co-crystals of FH viz. Fluoxetine hydrochloride-maleic acid (FH-MA), Fluoxetine hydrochloride-glutaric acid (FH-GA), Fluoxetine hydrochloride-L-tartaric acid (FH-LTA) and Fluoxetine hydrochloride-DL-tartaric acid (FH-DLTA) were obtained from screening experiments. Physical characterization showed that they have unique crystal morphology, thermal, spectroscopic and X-ray diffraction properties. Solubility and dissolution studies showed that Fluoxetine hydrochloride-maleic acid co-crystal possess high aqueous solubility in distilled water, pH 4.6, 7.0 buffer solutions and dissolution rate in distilled water than that of pure drug. Co-crystal formation approach can be used for ionic API to tailor its physical properties.

Formulation development of carvedilol compression coated tablet.

PURPOSE: The aim of present research was to produce carvedilol compression coated tablet to provide biphasic drug release. METHOD: A compressed coated tablet made of a sustained release core tablet and an immediate release coat tablet. Both the core and the coat contained carvedilol. The sustained release effect was achieved with polymers (HPMC K4M and PEO WSR 205) to modulate the release of the drug. The powder blends for core and coat tablets were evaluated for angle of repose, bulk density, compressibility index, and drug content. Compressed coated tablets were evaluated for thickness, diameter, weight variation test, drug content, hardness, friability, disintegration and in vitro release studies. RESULT: The powder blends showed satisfactory flow properties, compressibility, drug content and all the tablet formulations showed acceptable pharmaco-technical properties. Carvedilol contained in the fast releasing component was released within 3 min, whereas the drug in the core tablet was released at different times up to 24 h, depending on the composition of the matrix tablet. The mechanism of drug release was fickian diffusion or anomalous behavior. DISCUSSION: Batch F7, containing 10 mg PEO WSR 205 and 5 mg HPMC K4M, showed maximum similarity with theoretical profile and zero order drug release kinetic.

Simultaneous Estimation of Telmisartan, Chlorthalidone, Amlodipine Besylate and Atorvastatin by RP-HPLC Method for Synchronous Assay of Multiple FDC Products Using Analytical FMCEA-Based AQbD Approach.

Numerous reversed-phase high-pressure liquid chromatography (RP-HPLC) and high-performance thin-layer chromatography (HPTLC) techniques have been published for the estimation of fixed-dose combinations (FDCs) of telmisartan (TEL). No published literature has been reported to date which described the synchronous estimation of FDCs of TEL using a single chromatography condition. Hence, the RP-HPLC method has been developed and validated for synchronous analysis of FDCs of TEL using an enhanced analytical quality by design (AQbD) approach to save time, cost and solvent for analysis. The implementation of AQbD was initiated with the identification of failure modes (FMs) using the Ishikawa diagram, and their critical effect analysis was carried out by risk priority number ranking and filtering method. The identified critical FMs were optimized by design of experiments-based response surface modeling using the Box-Behnken design. The method operable design region was navigated and control strategy was framed to mitigate the risk of critical FM. The RP-HPLC method was developed using Shim-Pack octadecyl silane C18 column and acetonitrile: 1.0%v/v triethylamine (pH 6.5 adjusted using perchloric acid; 42:58, %v/v). The developed method was found to be validated as per the International Council For Harmonization Q2 (R1) guideline. The method was applied for the synchronous assay of seven different FDCs of TEL and assay results were found in good compliance with the respective labeled claim.

Method Greenness Profile Assessment to AQbD-Driven Stability Indicating HPTLC Method for Estimation of Aripiprazole Using Screening Design and Response Surface Modeling.

BACKGROUND: According to the literature review, organic solvents such as methanol, acetonitrile, toluene, and carbon tetrachloride have been used for the chromatographic analysis of aripiprazole (APZ). The green chemistry approach recommends these organic solvents are unsafe for analysts and the environment and should be avoided or minimized in chromatographic analysis. OBJECTIVE: Hence, the stability-indicating assay method (SIAM) has been developed for the estimation of aripiprazole using safe organic solvents. METHODS: The quality risk management was started with risk identification, which was followed by risk assessment. By the risk assessment process, seven analytical risk factors (ARFs) were found to be potentially risky for method development. Further risk analysis was done by Taguchi OA design for the study of the main effect of ARF on resolution between the peaks. Design of experiments (DoE)-based response surface modeling (RSM) was performed by central composite design. Method operable design region (MODR) was navigated for resolution between peaks more than 1.0 for risk control. After navigation of the MODR, a risk review was done by validation of the design model for SIAM. RESULTS: Control strategy was set for ARFs and separation was carried out on the precoated aluminum plate with silica gel 60 F254 using ethyl acetate-ethanol (8.0 + 2.0, v/v) as the mobile phase keeping 15 min saturation time. The developed method was validated as per the International Council for Harmonisation (ICH) Q2 (R1) guideline. The developed SIAM was applied for the assay of aripiprazole in its tablet, and results were found in agreement with the labeled claim. CONCLUSIONS: The organic solvents ethyl acetate and ethanol used in chromatographic analysis of APZ are recommended as safe organic solvents by the ICH Q3C guidelines. The method greenness profiles of developed and published methods were evaluated by national environmental method index (NEMI) and analytical greenness (AGREE) methods. The developed method was found to be safe and green for chromatographic analysis of APZ. HIGHLIGHTS: Development of a green, robust, accurate, and precise stability-indicating HPTLC method for estimation of APZ. The quality risk management (QRM) and DoE-based analytical quality by design (AQbD) approach was implemented in support of the green analytical chemistry concept. Estimation of greenness profile of method by NEMI and AGREE methods.

Principles of White Analytical Chemistry and Design of Experiments to Development of Stability-Indicating Chromatographic Method for the Simultaneous Estimation of Thiocolchicoside and Lornoxicam.

BACKGROUND: A variety of chromatographic methods have been published for the stability evaluation of thiocolchicoside (THC) and lornoxicam (LNX). Nevertheless, the development of chromatographic methods requires the use of neurotoxic and teratogenic organic solvents that are detrimental to the environment and harmful to human life. OBJECTIVES: Using the principles of design of experiments (DoE), a novel white analytical chemistry-driven stability-indicating high-performance thin-layer chromatographic (SI-HPTLC) method has been developed for the concurrent stability study of THC and LNX. To protect the environment and human life, the stability-indicating HPTLC method was developed using safe organic solvents. METHOD: Potential analytical method risk parameters (AMRPs) and analytical method performance attributes (AMPAs) were screened using the fractional factorial design. The response surface analysis and optimization of critical AMRPs and AMPAs was carried out using full factorial design. Navigation of the method operable design region (MODR) was used to develop the SI-HPTLC technique. The developed method was validated in accordance with the International Council for Harmonization (ICH) Q2 (R1) guideline. RESULTS: The developed method's greenness was evaluated using the AGREE (Analytical Procedure Greenness) tool and ESA (Eco-Scale Assessment). The Blue (B) model was used to assess the proposed method's cost and time efficiency and user-friendliness. For the stability studies of THC and LNX, the 12 principles of WAC (white analytical chemistry) were used to evaluate the published and proposed chromatographic techniques. CONCLUSIONS: Compared to previously published chromatographic techniques for studying the stability of THC and LNX, the suggested approach was found to be more affordable, environmentally friendly, and user-friendly. HIGHLIGHTS: The development of a stability-indicating HPTLC method using a novel white analytical chemistry approach and organic solvents with low toxicity potential. Application of the developed method for analysis of the forced degraded sample and fixed-dose combinations of THC and LNX.

Multivariate Analysis and Response Surface Modeling to Green Analytical Chemistry-Based RP-HPLC-PDA Method for Chromatographic Analysis of Vildagliptin and Remogliflozin Etabonate.

BACKGROUND: The fixed-dose combination (FDC) of vildagliptin (VDG) and remogliflozin etabonate (RGE) is used as antidiabetic medicine. Numerous reverse phase high-pressure liquid chromatographic (RP-HPLC) methods have been reported for the estimation of VDG and RGE using toxic organic solvents such as acetonitrile and methanol. These organic solvents are also hazardous to the environment. OBJECTIVE: Hence, the robust and green analytical chemistry-based RP-HPLC-PDA method has been developed for chromatographic analysis of VDG and RGE for the safety of analysts and protection of the environment. METHOD: The multivariate analysis has been carried out for the identification of critical method risk parameters (CMRPs) and critical method performance attributes (CMPAs) using principal component analysis (PCA). The identified CMRPs and CMPAs were linked with each other for optimization of the RP-HPLC-PDA method using DoE-based response surface modeling. The analytical design space (ADS) has been explored for robust chromatographic analysis of VDG and RGE. RESULTS: The chromatographic analysis of VDG and RGE has been carried out using Shim-Pack C18 column (250 mm L, 4.6 mm ID, 5.0 µm PS) and isopropyl alcohol-0.1% (v/v) formic acid (FA) in water (45 + 55, v/v, pH -3.5). The developed method has been validated in accordance with ICH Q2 (R1) guidelines. The method has been applied for the assay of VDG and RGE in their FDCs. The results of the assay were found in compliance with the labeled claims. CONCLUSIONS: The developed RP-HPLC-PDA method did not include any toxic or carcinogenic solvents. Hence, it is safe for analysts and the environment. The greenness profiles of the published and proposed RP-HPLC methods were evaluated by the national environmental method index (NEMI) scale, and the analytical greenness scores were calculated using the AGREE software. The developed method can be used as an eco-friendly tool in the pharmaceutical industry for routine analysis and quality control of FDCs of VDG and RGE. HIGHLIGHTS: Development of a green and robust RP-HPLC method for the estimation of VDG and RGE using safe organic solvents. The analytical quality by design (AQbD) approach has been implemented in the development of a method to minimize solvent wastage. The method was applied for the assay of FDCs of VDG and RGE.

Red, Green, and Blue Model-Based Assessment and Principles of White Analytical Chemistry to Robust Stability-Indicating Chromatographic Estimation of Thiocolchicoside and Diclofenac Sodium.

BACKGROUND: White analytical chemistry (WAC) is a recent approach for evaluating analytical procedures based on their effectiveness in validating results, capacity to be environmentally friendly, and economic effectiveness. OBJECTIVE: The detection of diclofenac sodium (DCF) and thiocolchicoside (THC) simultaneously has been established using a WAC-driven stability-indicating chromatographic method (SICM). METHODS: For the concurrent stability study of THC and DCF, the suggested chromatographic technique was developed employing safe and environmentally acceptable organic solvents. To identify critical analytical method parameters (AMPs) and analytical quality attributes (AQAs), a design of experiments (DoE)-based screening design was applied. For the DoE-based response surface modelling (RSM) of critical AMPs and AQAs, the Box-Behnken design (BBD) was employed. RESULTS: A robust SICM was developed by navigating the analytical design space for simultaneous estimation of THC and DCF. IR, NMR, and mass spectral data were used to characterize the degradation products. Red, green, and blue (RGB) models were used to evaluate the suggested method's validation effectiveness, greenness power, and economic efficiency and compared to published chromatographic techniques. The effectiveness of the chromatographic method's validation concerning the International Council for Harmonization (ICH) Q2 (R1) guideline was evaluated using the red model. The analytical greenness (AGREE) evaluation tool and eco-scale assessment (ESA) approach were used to evaluate the green model's methodology. The blue model-based assessment was carried out for comparison of simplicity of instruments handling, cost, and time during sample analysis. The red, blue, and green scores of the techniques were averaged to arrive at the white score of the suggested and reported methods. CONCLUSION: For the concurrent stability study of THC and DCF, the suggested technique was shown to be validated, environmentally friendly, and cost effective. The suggested approach could be a cost-effective and environmentally friendly analytical technique for determining the stability and monitoring the quality of fixed-dose combinations (FDC) of THC and DCF. HIGHLIGHTS: Stability-indicating HPTLC method was developed for concomitant analysis of THC and DCF using concepts of DoE and WAC.

Green and Sustainable Analytical Chemistry-Driven Chromatographic Method Development for Stability Study of Apixaban Using Box-Behnken Design and Principal Component Analysis.

Apixaban (APX) is a novel anti-coagulant drug approved by USFDA. According to referred literature, numerous chromatographic methods such as RP-HPLC and high-performance thin-layer chromatography have been published for the stability study of APX. But these chromatographic methods have been developed using toxic organic solvents that are hazardous to the environment and unsafe for analysts. Hence, green and sustainable analytical chemistry-driven chromatographic method has been developed for the stability study of APX using safe organic solvents for the safety of analysts and the protection of the environment. APX was subjected to forced degradation for the development of a stability-indicating assay method. The method development was carried out by the implementation of chemometric and DoE approaches for minimizing solvent wastage. Principal component analysis was applied for the identification of critical method risk variables (MRVs) and method performance attributes. DoE-based response surface modelling was applied for the optimisation of critical MRVs. The greenness profile scales of published and developed chromatographic methods have been assessed by NEMI and AGREE methods for the estimation of APX. The developed method was found to be more eco-friendly and robust than the published chromatographic methods for the estimation of APX.