Innovare Academic Sciences: E-Journals
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EFFECT OF MINERALOCORTICOID RECEPTOR ANTAGONISTS ON CARDIOVASCULAR MORTALITY IN ADULTS WITH HEART FAILURE: AMETA-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS
No full textObjective: To evaluate the effect of mineralocorticoid receptor antagonists on cardiovascular mortality in adults with heart failure using evidence from randomized controlled trials.
Methods: A systematic review and meta-analysis of randomized controlled trials was conducted in accordance with PRISMA 2020 guidelines. Electronic databases, including PubMed, Scopus, Google Scholar, and the Cochrane Central Register of Controlled Trials were searched for eligible studies. Trials enrolling adult patients with heart failure and comparing MRAs with placebo were included. Cardiovascular mortality was the primary outcome. Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated for individual studies and pooled using an inverse-variance fixed-effect model. Statistical heterogeneity was evaluated using Cochran’s Q test and the I² statistic. Risk of bias was assessed using the Cochrane Risk of Bias tool, and certainty of evidence was evaluated using the GRADE framework.
Results: Three large, double-blind randomized controlled trials comprising 11,032 patients met the inclusion criteria. Treatment with MRAs was associated with a significant reduction in cardiovascular mortality compared with placebo. The pooled analysis demonstrated a 20% relative reduction in cardiovascular mortality (pooled RR = 0.80; 95% CI: 0.73–0.86). No significant heterogeneity was observed among the included studies (I² = 0%). All trials were judged to have a low risk of bias, and the certainty of evidence for the primary outcome was rated as high.
Conclusion: Mineralocorticoid receptor antagonists significantly reduce cardiovascular mortality in patients with heart failure. These findings provide high-certainty evidence supporting their use as an essential component of guideline-directed medical therapy
DEVELOPMENT AND VALIDATION OF UV SPECTROPHOTOMETRIC METHOD FOR EPICATECHIN ESTIMATION WITH SOLUBILITY ANALYSIS
No full textObjectives: This study aimed to develop and validate an ultraviolet (UV) spectrophotometric method for the accurate and reproducible quantification of epicatechin in bulk form. In addition, the solubility profile of epicatechin in various pharmaceutical solvents and oils was systematically investigated to support formulation development.
Methods: Method development was carried out using pure epicatechin with methanol as the solvent. The method was validated according to international council for harmonization guidelines by evaluating linearity, precision (intra-day and inter-day), accuracy, limit of detection, limit of quantification, and robustness. Solubility studies were performed by equilibrating excess epicatechin with selected solvents (methanol, isopropyl alcohol, chloroform, ethyl acetate, water, and 1-butanol) and oils (castor oil, coconut oil, eucalyptus oil, olive oil, and clove oil), followed by quantitative analysis using UV spectrophotometry. Statistical analysis was applied where applicable, with significance considered at p<0.05.
Results: The developed method exhibited excellent linearity over the studied concentration range (R2=0.9982), with high precision (percent relative standard deviation [%RSD]<3.1%), acceptable accuracy (recovery 98.5–106.3%), and robust performance (%RSD<2.0%). All validation parameters were statistically acceptable (p<0.05). Solubility studies revealed that methanol demonstrated significantly higher solubility for epicatechin (12.33±0.05 mg/mL) compared with other solvents (p<0.05), followed by isopropyl alcohol and chloroform. Among the oils evaluated, castor oil (4.75±0.02 mg/mL) and coconut oil (3.89±0.01 mg/mL) showed significantly greater solubilizing capacity than other oils (p<0.05).
Conclusion: The validated UV spectrophotometric method is reliable, economical, and suitable for routine quantification of epicatechin in pharmaceutical and research applications. Furthermore, the statistically significant solubility findings (p<0.05) provide valuable guidance for the rational formulation design of epicatechin-based dosage forms
DEVELOPMENT AND VALIDATION OF A SELECTIVE ELECTRO SPRAY IONIZATION – LIQUID CHROMATOGRAPH TANDEM MASS SPECTROMETRY METHOD FOR SIMULTANEOUS DETERMINATION OF SEMAGLUTIDE AND EMPAGLIFLOZIN IN HUMAN PLASMA
No full textObjective: The objective of the study was to develop a method capable of simultaneously estimating semaglutide and empagliflozin used in combination for treating Diabetes.
Methods: A structured protein precipitation extraction technique was used for the estimation of semaglutide and empagliflozin. The two compounds were separated on a Zorbax C18 (50 mm × 2.1 mm, 5 μ Particle size) column, with a positive polarity Electro Spray Ionization on a Liquid chromatograph with Tandem Mass Spectrometry instrument. Verapamil was employed as an internal standard for this estimation, which was carried out through a multiple reaction monitoring method and a gradient program utilizing acetonitrile and 0.1% formic acid in water as mobile phases to achieve a separation in 2.5 min.
Results: The method established was performing linearly over a working range of 1.00–1000 ng/mL for semaglutide (r2>0.98) and 0.51–500 ng/mL for empagliflozin (r2>0.98) in human plasma. The validation parameters, including specificity, selectivity, precision, accuracy, recovery, matrix effects and stability, were within acceptable limits. The stability was established in compliance with the International Council for Harmonization guideline M10 on Bioanalytical method validation.
Conclusion: This method was selective and with suitable sensitivity at the 1.00 ng/mL and 0.50 ng/mL Lower Limit of Quantification employed for semaglutide and empagliflozin. It can be utilized for estimation in human plasma and will facilitate further application to bioequivalence and exploratory formulation studies for the combination of these two drugs in pharmaceutical dosage form
PRE-CLINICAL NEUROPHARMACOLOGY EFFICACY AND TOXICITY OF AVENIA SATIVAUM IN RATS
No full textObjective: The present study investigates the neuropharmacological potential of methanolic and ethanolic leaf extracts of Avena sativa L. in experimental models of depression.
Methods: Acute toxicity evaluation revealed no mortality, morbidity, or behavioral abnormalities following a single oral dose of 2000 mg/kg, confirming the safety of both extracts. Based on this, 100 and 200 mg/kg doses were selected for behavioral assessment. Antidepressant-like activity was evaluated using the forced swimming test (FST) and tail suspension test (TST).
Result: Rats treated with methanolic extract at 100 mg/kg (arteriovenous methanolic [AVM]-100) exhibited significantly reduced immobility times in both FST (46.2 s) and TST (50.7 s), closely approximating the standard drug (39.6 s and 43.0 s, respectively,**p<0.001). Higher doses (AVM- 200) and ethanolic extracts (arteriovenous ethanolic [AVE]-100 and AVE-200) showed moderate reductions, suggesting a non-linear dose-response relationship. Locomotor activity analysis further supported the antidepressant profile of AVM-100, which showed the highest count (680) without signs of hyperactivity, indicating reversal of psychomotor retardation. The observed effects are likely mediated by neuroactive phytochemicals, such as avenanthramides and flavonoids, known to modulate neurotransmitter systems and stress-response pathways.
Conclusion: Overall, the findings highlight the therapeutic promise of A. sativa methanolic extract, particularly at 100 mg/kg, as a safe and effective plant-based candidate for managing depressive disorders
PHYTOCHEMICAL PROFILING USING HIGH-RESOLUTION LIQUID CHROMATOGRAPHY-MASS SPECTROMETRY AND EVALUATION OF THE IN VITRO ANTIOXIDANT AND ANTIDIABETIC POTENTIAL OF HYDROALCOHOLIC EXTRACT OF IPOMOEA CAIRICA LEAVES
No full textObjective: This paper examines the phytochemical composition and biological functions of hydroalcoholic extract of Ipomoea cairica (HEIC) leaf, which is a perennial herb traditionally used in the treatment of inflammation, diarrhea, and febrile rashes.
Methods: A range of bioactive compounds was detected with the help of high-resolution liquid chromatography-mass spectrometry, among which flavonoid and alkaloid compounds, phenolic acids, and glycosides are well-known as antioxidants and antidiabetics.
Results: HEIC in vitro antioxidant capacity was assessed using a series of assays, which showed that the solution has a dose-dependent radical-scavenging activity, but the activity of this compound is lower than the one of ascorbic acid. More so, the extract had moderate inhibitory effects on alpha-amylase and alpha-glucosidase enzymes with IC50 values of 130.67 μg/mL and 212 μg/mL, respectively, suggesting its possible clinical use in the control of postprandial glucose concentration.
Conclusion: Major phytochemicals, including quercetin 3-rhamanoside-7-glucoside, rutin, physalis K, and 1,4-Di-O-caffeoylquinic acid, were associated with the therapeutic value of the extract. These results support conventional uses of I. cairica in herbal medicine and emphasize its potential in the preparation of natural antioxidants and antidiabetic agents
EVALUATING THE ANTI-INFLAMMATORY ACTIVITY OF ETHYL ACETATE AND METHANOL EXTRACTS OF LORANTHUS EUROPAEUS SEEDS IN RAT MODELS OF EXPERIMENTALLY INDUCED CHRONIC INFLAMMATION: A COMPARATIVE STUDY WITH DEXAMETHASONE
No full textObjective: Loranthus europaeus is a parasitic plant that lives on the branches of trees. The present study aimed to evaluate the anti-inflammatory effects of two different extracts on chronic inflammation induced by cotton pellets in rats.
Methods: Loranthus seed was extracted by maceration with absolute methanol, in which dry Loranthus seeds were triturated in a mortar and macerated with 500 mL of methanol. After 24 h, the mixture was filtered, and the residue was re-extracted. The filtrates were combined and dried under vacuum. The mixture was mixed with 100 mL of distilled water and fractionated by petroleum ether and ethyl acetate using 70 mL × 3 times each. The organic fractions were dried, filtered, and evaporated to dryness. Ethyl acetate and methanol fractions at a dose of 100 mg/kg were tested for suppressive effect for chronic inflammation using the cotton pellet-induced granuloma technique compared with dexamethasone.
Results: Both fractions of L. europaeus seeds showed a significant decrease in the weight of exudate and weight of granuloma when compared with the negative control. Furthermore, both fractions showed a significant increase in these two parameters when compared to the standard group (dexamethasone group).
Conclusion: The present study showed that the ethyl acetate fraction has a significant suppressive effect on chronic inflammatory processes in rats when compared with the methanol fraction
REVERSED PHASE-HIGH-PERFORMANCE-LIQUID CHROMATOGRAPHY METHOD FOR THE ESTIMATION OF MAGNOLOL IN SELF-NANO-EMULSIFYING DRUG DELIVERY SYSTEM
No full textObjectives: Reversed-phase high-performance liquid chromatography was used to produce a simple, accurate, and precise method for the estimation of Magnolol (MO) in self-nano-emulsifying drug delivery system.
Method: Analysis of this method was carried out using reverse phase Nucleodur C-18 column. For this study Mobile phase used was acetonitrile: H2O (90:10% v/v), the flow rate was 1.0 mL/min, chromatogram of MO was determined at wavelength 290 nm, and sharp peak was obtained at retention time of 3.496 min. Validation of the developed method was done according to International Conference on HarmonizationQ2 (R1) guidelines.
Results: MO showed linearity at 2–10 μg/mL with R2 of 0.9983. The % mean recovery was determined to be 95.01%, suggesting that the approach was accurate, and from the relative standard deviation, which was found to be varying from 0.53% to 1.96% for both intra-day and inter-day precision, that is, clearly <2%, indicates that the method was precise. It was observed that the detection and quantification limits, that is, limit of quantification and limit of detection, were, respectively, 0.50 and 1.52 μg/mL. Finally, for the developed method, Robustness study was performed by doing small variations in pH, flow rate, ratio of mobile phase, and the result showed that the developed method was robust, as the percentage relative standard deviation and % recovery were under a specific limit.
Conclusion: This indicates that the method that was developed was accurate, linear, précised and robust. Furthermore, it can be used to estimate MO in Pharmaceutical formulations
CHEMICAL COMPOSITION, IN VITRO WOUND HEALING ACTIVITY, AND IN SILICO DOCKING EVALUATION OF ESSENTIAL OILS FROM CITRUS MAXIMA (BURM.) MERR LEAVES AND PEELS
No full textObjective: The purpose of this study was to investigate antibacterial and antioxidant activities, and evaluate in vitro wound healing potential via fibroblast proliferation assay of Citrus maxima leaves oil (MLEO) and C. maxima peels oil (MPEO), determine chemical constituents, and predict the chemical component responsible for antibacterial properties.
Methods: This citrus oil was obtained through hydrodistillation. The analysis of chemical composition was obtained using gas chromatography–mass spectrometry (GC-MS) spectroscopy. In vitro wound healing using MTT assays against fibroblast cells, antioxidant activities were evaluated through ABTS assay, and antibacterial activities using the broth microdilution method against Staphylococcus aureus (ATCC 25423) and Escherichia coli (ATCC 25422). The molecular docking of main chemical compounds was evaluated using PBP 1a (3UDI) and PBP 2a (1MWT) proteins.
Results: GC-MS revealed that D-limonene was dominant in the peels, while 3-carane was dominant in the leaves. The in vitro wound healing activity showed that MLEO and MPEO enhanced the number of fibroblast cells with values of 103.31±3.53% and 100.09±2.28%, respectively, at a concentration of 0.1 μg/mL. MLEO exhibited a lower IC50 value than MPEO, with avalue of 251.97±3.34 μg/mL. MLEO also exhibited strong antibacterial activity, with minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of 3.125 mg/mL against S. aureus, and MIC of 6.25 mg/mL and MBC of 12.5 mg/mL against E. coli. Molecular docking analysis indicated that 3-carene had the strongest binding affinities on PBP 1a protein (−6.222 kcal/mol) and caryophyllene on PBP 2a protein (−6,663 kcal/mol).
Conclusion: This study confirms that MLEO showed the potential for wound healing, antioxidant, and antibacterial activity
NOVEL MEFENAMIC ACID-ANTIBIOTIC COMBINATIONS AS POTENTIAL INHIBITORS OF SARS-COV-2 MAIN PROTEASE
No full textObjective: The ongoing search for effective COVID-19 treatments has driven interest in drug repurposing and hybrid drug design strategies. This study aimed to develop and evaluate novel mefenamic acid–antibiotic hybrids as potential inhibitors of the SARS-CoV-2 main protease (Mpro).
Methods: Eight hybrid molecules were rationally designed and analyzed using molecular docking and in silico ADME evaluations to predict their binding affinity, stability, pharmacokinetic, and pharmacodynamic behaviour.
Results: Eight mefenamic acid–antibiotic hybrids were evaluated for their potential to inhibit SARS-CoV-2 Mpro. All hybrids demonstrated stronger binding affinity than mefenamic acid (MEF) alone, with the MEF–cephalexin (MEF–CEX) conjugate showing the most favorable binding energy (–7.6 kcal/mol), indicating enhanced complex stability due to the cephalosporin scaffold. ADME predictions revealed moderate pharmacokinetic properties across the series, and the MEF–ciprofloxacin (MEF–CIP) hybrid displayed notable blood–brain barrier permeability despite one Lipinski rule violation.
Conclusion: The findings highlight mefenamic acid–antibiotic hybrids, particularly cephalosporin-based derivatives, as promising multifunctional candidates with combined anti-inflammatory and antiviral potential against SARS-CoV-2. Further preclinical validation is warranted to optimize their pharmacological and safety profiles for potential therapeutic application
NAVIGATING ANDA APPROVAL: A COMPREHENSIVE ANALYSIS OF SUBMISSION STRATEGIES AND POLICIES AND PROCEDURES FOR DEFICIENCY HANDLING
No full textObjective: This review provides a comprehensive understanding of regulatory expectations for generic drug approval in the United States. It highlights essential submission components, evaluation procedures, and common scientific and administrative issues that may lead to Refuse-to-Receive decisions. The review aims to guide applicants in improving submission quality and streamlining regulatory assessment.
Methods: Information was collected from official guidance documents, federal regulations, national generic drug program performance reports, and peer-reviewed literature related to regulatory science and generic drug development. Publications addressing filing requirements, laboratory and manufacturing standards, comparative clinical study principles, and deficiency management strategies were included, while outdated or irrelevant sources were excluded.
Results: This review summarizes the administrative, scientific, and technical requirements for complete generic drug submissions. It describes regulatory evaluation procedures, common deficiencies identified during review, and mechanisms for information requests. Although recent trends indicate improved submission quality and reduced approval timelines, gaps in scientific and technical documentation continue to limit first-cycle approvals.
Conclusion: Structured ANDA submissions supported by robust scientific evidence and early engagement with regulatory authorities can significantly reduce review delays and Refuse-to-Receive outcomes. Ensuring data completeness, adherence to regulatory guidelines, and systematic documentation from the early development stage improves the likelihood of timely approval for generic medicines