Quality control methods for fruit extracts of Kigelia africana using high performance thin layer chromatography.

Kigelia africana is a tree native to Africa but also found in eastern and southern parts of India with reported anti-bacterial, anti-inflammatory, and immunomodulatory activities. Verbascoside, caffeic acid and ferulic acid are important markers for the quality control of the plant. Two different HPTLC methods were developed and validated; method - 1 for estimation of verbascoside and caffeic acid while method - 2 for estimation of caffeic acid and ferulic acid. Developed methods were applied to the methanolic fruit extract to determine the quantities of markers. Both methods were found to be linear, specific, precise, accurate, sensitive and robust. Results indicated that both methods can be used for quantitative determination of verbascoside, caffeic acid and ferulic acid in fruit extract. The developed methods may be utilised as a part of the quality control and standardisation for the raw material and extracts of Kigelia africana and can also aid to chromatographic fingerprinting of the plant.

Immunomodulatory Therapy in Head and Neck Squamous Cell Carcinoma: Recent Advances and Clinical Prospects.

The immune system plays a significant role in the development, invasion, progression, and metastasis of head and neck cancer. Over the last decade, the emergence of immunotherapy has irreversibly altered the paradigm of cancer treatment. The current treatment modalities for head and neck squamous cell carcinoma (HNSCC) include surgery, radiotherapy, and adjuvant or neoadjuvant chemotherapy which has failed to provide satisfactory clinical outcomes. To encounter this, there is a need for a novel or targeted therapy such as immunological targets along with conventional treatment strategy for optimal therapeutic outcomes. The immune system can contribute to promoting metastasis, angiogenesis, and growth by exploiting the tumor's influence on the microenvironment. Immunological targets have been found effective in recent clinical studies and have shown promising results. This review outlines the important immunological targets and the medications acting on them that have already been explored, are currently under clinical trials and are further being targeted.

Impact of cetuximab plus cisplatin alone and cetuximab plus cisplatin and paclitaxel regimen on humanistic outcome in head and neck cancer.

BACKGROUND: The prevalence of head and neck cancer (HNC) is increasing rapidly, and the prognosis is poor in the advance stage. For the patient suffering from advance stage HNC, the improvement in quality of life and decrease mortality remain as the mainstay of treatment. The aim was to assess the change in quality-adjusted life-years (QALYs) in recurrent or metastatic HNC patients receiving cetuximab plus cisplatin and cetuximab plus cisplatin-paclitaxel. METHODS: It was a single-centric prospective-observational study. Patients were divided into two cohorts based on the chemotherapy regimens they were prescribed. Patients in cohort 1 were prescribed with cetuximab and cisplatin and in cohort 2 were prescribed with cetuximab, cisplatin, and paclitaxel. The QALYs were the primary outcome of the study, and it was calculated using EQ-5D-5L instrument. Patients were followed until the completion of the therapy, i.e., six chemotherapy cycles. The statistical analysis was carried out using SPSS for descriptive and inferential analysis. RESULTS: Amongst 175 patients screened, 100 patients were enrolled which further distributed in cohorts 1 and 2 equally. The mean QALYs were 0.016 and 0.017 at the time of diagnosis, i.e., before initiation of chemotherapy for patients in cohorts 1 and 2, respectively. At every chemotherapy cycle, the QALYs were calculated. After the completion of six chemotherapy cycles, the mean QALYs were 0.029 and 0.032 for patients in cohorts 1 and 2, respectively. CONCLUSION: The three-drug therapy consisting of cetuximab, cisplatin, and paclitaxel has shown significant improvement in patients' QALYs compared to two-drug regimens of cetuximab and cisplatin. Thus, if the therapy consisted of three-drug regimen is used instead of two-drug regimen, it will have a positive impact on humanistic outcome in recurrent or metastatic HNC patients.

A review of efficacy and safety of cetuximab and bevacizumab-based monoclonal antibodies in head and neck cancer.

A combination of monoclonal antibodies prescribed along with the conventional standard of care has a potential to provide significant improvement in patients suffering from head and neck cancer. This combination has also shown a significant decrease in toxicities and improved overall quality of life. Cetuximab acts by inhibiting the human epidermal growth factors as its overexpression in head and neck tumours that are responsible for treatment failure, resistance, and metastasis. Whereas, bevacizumab acts by inhibiting the vascular endothelial growth factor since its overexpression leads to induction of tumour angiogenesis. Current research has not shown any remarkable beneficial effect in disease outcomes. Thus, the addition of these monoclonal antibodies to the standard regimen for head and neck cancer can be considered a prospect that might be beneficial. Cetuximab has already been included as an option under special recommendations in recurrent/metastatic head and neck cancer by NCCN in a platinum-based regimen as well as in combination with radiation therapy. This review outlines the applicability of cetuximab and bevacizumab in the treatment of head and neck cancer as well as the clinical trials performed that give an idea about the efficacy and safety of these monoclonal antibodies. Based upon the literature reviewed, it can be deduced that immunotherapy is to be adopted and different targets are to be explored in it in order to combat head and neck cancer. Currently, immunotherapeutic drugs of two major targets have been discussed. These agents are even effective in combination with other therapeutic modalities that are not being able to achieve desirable outcomes due to issues such as resistance and toxicities. Thus, newer targets as well as newer agents acting on established targets are to be explored in order to improve disease outcomes.

In-silico Computational Investigations of AntiViral Lignan Derivatives as Potent Inhibitors of SARS CoV-2.

Due to alarming outbreak of pandemic COVID-19 in recent times, there is a strong need to discover and identify new antiviral agents acting against SARS CoV-2. Among natural products, lignan derivatives have been found effective against several viral strains including SARS CoV-2. Total of twenty-seven reported antiviral lignan derivatives of plant origin have been selected for computational studies to identify the potent inhibitors of SARS CoV-2. Molecular docking study has been carried out in order to predict and describe molecular interaction between active site of enzyme and lignan derivatives. Out of identified hits, clemastatin B and erythro-strebluslignanol G demonstrated stronger binding and high affinity with all selected proteins. Molecular dynamics simulation studies of clemastin B and savinin against promising targets of SARS CoV-2 have revealed their inhibitory potential against SARS CoV-2. In fine, in-silico computational studies have provided initial breakthrough in design and discovery of potential SARS CoV-2 inhibitors.

Simultaneous Estimation of Six Nitrosamine Impurities in Valsartan Using Liquid Chromatographic Method.

BACKGROUND: Nitrosamine impurities are potent carcinogens in animals and probable carcinogens in humans. There is a need for effective analytical methods to detect and identify various nitrosamine impurities, and to develop rapid solutions to ensure the safety and quality of the drugs. OBJECTIVE: A liquid chromatographic method was developed for estimation of six nitrosamine impurities in valsartan. METHODS: The developed method employed: a C18 (250 × 4.6 mm, 5 µm) column as a stationary phase; a combination of acetonitrile, water (pH 3.2 adjusted with formic acid), and methanol with gradient elution as mobile phase; and 228 nm as the detection wavelength. The developed method was validated as per International Conference on Harmonization Q2(R1) guidelines. The method was successfully applied to estimate six nitrosamine impurities in valsartan API (active pharmaceutical ingradient) and formulation (tablets). RESULTS: The method was able to separate each impurity and valsartan with resolved and sharp peaks. Results indicated that the developed method is linear in selected ranges (coefficient of regressions >0.9996), precise (RSD <2%), accurate (recovery in a range of 99.02-100.16%), sensitive (low detection and quantitation limits), and specific for estimation of each impurity in valsartan. Assay results were in agreement with the spiked amount of each impurity. CONCLUSION: The developed method can be applied for simultaneous estimation of six nitrosamine impurities in valsartan raw material, tablets, and fixed dose combination at very low levels. HIGHLIGHTS: Development, validation, and application of a HPLC method for the estimation of six nitrosamine impurities in valsartan API and formulation samples.

Development and Validation of Stability-indicating RP-HPLC Method for Estimation of Pranlukast Hydrate in its Laboratory Mixture.

Pranlukast hydrate is an anti-asthmatic drug and used in the treatment of acute asthma. Stability-indicating RP-HPLC method for pranlukast hydrate has been developed and validated. The reverse phase high performance liquid chromatographic method was developed using Shimadzu Column: Kromosil 100 C18 (150 mm × 4.6 mm × 5 µm) and mobile phase Acetonitrile: 0.1% Glacial acetic acid (85: 15% v/v). Eluent was monitored with UV-detector at 262 nm with a flow rate of 0.5 mL/min, temperature maintained at 30°C. Stress testing was carried out in acidic, alkaline, oxidative, photolytic and dry heat degradation conditions. The method was validated as per the International Conference for Harmonization guidelines and includes specificity, accuracy, precision, linearity and limit of quantitation and detection parameters. A relative standard deviation <2% indicates the developed method was precise. The accuracy of the method was represented by recovery studies ranging between 99.41 and 99.72%. In acid, alkaline, oxidative stress conditions, pranlukast hydrate degrades significantly and in photolytic, dry heat, hydrolytic conditions remain stable. This proposed method is suitable for the analysis of pranlukast hydrate in its laboratory mixture.

Quality Risk Management-Based AQbD Approach to Development of VEER Chromatography Method for the Estimation of Multiple Combined Formulations of Anti-Hypertensive Drugs.

BACKGROUND: A number of chromatography methods for estimating combined dosage forms of telmisartan have been published in the literature, but each combined dosage form needs separate chromatography conditions for analysis. OBJECTIVE: The versatile, economical, eco-friendly, and robust chromatographic method has been developed for simultaneous estimation of multiple combined pharmaceutical dosage forms of anti-hypertensive drugs using the analytical quality by design approach based on principles of quality risk management (QRM) and design of experiment (DoE). METHOD: Analytical QRM was performed by identifying probable method risk parameters and risk assessment for the development of the method. DoE was performed by Taguchi Orthogonal Array (OA)  screening design and Box-Behnken response surface design using Design-Expert software (trial version). Chromatographic separation was performed using silica gel 60 GF254 as stationary phase and toluene-ethyl acetate-methanol-glacial acetic acid (5.5 + 2 + 1 + 0.2, v/v/v/v) as a mobile phase keeping saturation time of 15 min. The developed method was applied for the assay of six combined pharmaceutical dosage forms of anti-hypertensive drugs. RESULTS: The developed method was found to be validated for accuracy, precision, specificity, linearity, LOD, LOQ, and robustness as per ICH guideline. The results of the assay were found in good agreement with the labelled claim. CONCLUSIONS: The developed method can be applied for analysis and quality control of multiple combined dosage forms of telmisartan. HIGHLIGHTS: A QRM and DoE-based AQbD approach was applied for development of chromatography method for simultaneous estimation of multiple combined dosage forms of telmisartan. The developed method was successfully applied for simultaneous estimation of six different multiple combined dosage forms of temisrtan.

A decennary update on applications of metal nanoparticles (MNPs) in the synthesis of nitrogen- and oxygen-containing heterocyclic scaffolds.

Heterocycles have been found to be of much importance as several nitrogen- and oxygen-containing heterocycle compounds exist amongst the various USFDA-approved drugs. Because of the advancement of nanotechnology, nanocatalysis has found abundant applications in the synthesis of heterocyclic compounds. Numerous nanoparticles (NPs) have been utilized for several organic transformations, which led us to make dedicated efforts for the complete coverage of applications of metal nanoparticles (MNPs) in the synthesis of heterocyclic scaffolds reported from 2010 to 2019. Our emphasize during the coverage of catalyzed reactions of the various MNPs such as Ag, Au, Co, Cu, Fe, Ni, Pd, Pt, Rh, Ru, Si, Ti, and Zn has not only been on nanoparticles catalyzed synthetic transformations for the synthesis of heterocyclic scaffolds, but also provide an inherent framework for the reader to select a suitable catalytic system of interest for the synthesis of desired heterocyclic scaffold.

Simultaneous Estimation of Ofloxacin, Clotrimazole, and Lignocaine Hydrochloride in Their Combined Ear-Drop Formulation by Two Spectrophotometric Methods.

Two sensitive, accurate, and precise spectrophotometric methods have been developed and validated for the simultaneous estimation of ofloxacin (OFX), clotrimazole (CLZ), and lignocaine hydrochloride (LGN) in their combined dosage form (ear drops) without prior separation. The derivative ratio spectra method (method 1) includes the measurement of OFX and CLZ at zero-crossing points (ZCPs) of each other obtained from the ratio derivative spectra using standard LGN as a divisor, whereas the measurement of LGN at the ZCP of CLZ is obtained from the ratio derivative spectra using standard OFX as a divisor. The double divisor-ratio derivative method (method 2) includes the measurement of each drug at its amplitude in the double divisor-ratio spectra obtained using a standard mixture of the other two drugs as the divisor. Both methods were found to be linear (correlation coefficients of >0.996) over the ranges of 3-15, 10-50, and 20-100 µg/mL for OFX, CLZ, and LGN, respectively; precise (RSD of <2%); and accurate (recovery of >98%) for the estimation of each drug. The developed methods were successfully applied for the estimation of these drugs in a marketed ear-drop formulation. Excipients and other ingredients did not interfere with the estimation of these drugs. Both methods were statistically compared using the t-test.

Degradation Kinetics Study of Alogliptin Benzoate in Alkaline Medium by Validated Stability-Indicating HPTLC Method.

A rapid, sensitive, and stability-indicating high-performance thin-layer chromatographic method was developed and validated to study degradation kinetics of Alogliptin benzoate (ALG) in an alkaline medium. ALG was degraded under acidic, alkaline, oxidative, and thermal stress conditions. The degraded samples were chromatographed on silica gel 60F254-TLC plates, developed using a quaternary-solvent system (chloroform-methanol-ethyl acetate-triethyl amine, 9+1+1+0.5, v/v/v/v), and scanned at 278 nm. The developed method was validated per International Conference on Harmonization guidelines using validation parameters such as specificity, linearity and range, precision, accuracy, LOD, and LOQ. The linearity range for ALG was 100-500 ng/band (correlation coefficient = 0.9997) with an average recovery of 99.47%. The LOD and LOQ for ALG were 9.8 and 32.7 ng/band, respectively. The developed method was successfully applied for the quantitative estimation of ALG in its synthetic mixture with common excipients. Degradation kinetics of ALG in an alkaline medium was studied by degrading it under three different temperatures and three different concentrations of alkali. Degradation of ALG in the alkaline medium was found to follow first-order kinetics. Contour plots have been generated to predict degradation rate constant, half-life, and shelf life of ALG in various combinations of temperature and concentration of alkali using Design Expert software.

Development and Validation of Stability-Indicating HPTLC Method for Estimation of Naratriptan Hydrochloride in Its Pharmaceutical Dosage Form and Its Content Uniformity Testing.

The present research project involves development and validation of a stability-indicating HPTLC method for the estimation of naratriptan-HCl in their pharmaceutical dosage forms and its content uniformity testing. Naratriptan-HCl was subjected to alkaline, acidic, oxidative, neutral, thermal (dry heat) and photo-degradation conditions. The chromatographic separation was carried out using a precoated silica gel G 60 F254 TLC plate as the stationary phase and dichloromethane-toluene-methanol-triethylamine (4 : 4 : 2 : 1, v/v/v/v) as the mobile phase. The spots of NRT-HCl and its degradation products were detected at 290 nm. The Rf value of NRT-HCl was found to be 0.60 ± 0.02. The linearity was obtained in the range of 100-500 ng/spot. The limit of detection and limit of quantitation were found to be 6.07 ng/spot and 18.41 ng/spot, respectively. The percentage recovery was found in the range of 98.87-99.55%. NRT-HCl was degraded under acidic, alkaline and oxidative conditions while stable under photolytic, neutral and dry heat conditions. The developed method was applied for estimation of naratriptan-HCl in marketed formulations and its content uniformity testing.