Innovare Academic Sciences: E-Journals
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DOE-BASED FORMULATION AND CHARACTERIZATION OF NIFEDIPINE-LOADED SMEDDS EMBEDDED IN FAST DISSOLVING FILMS FOR IMPROVED ORAL BIOAVAILABILITY
No full textObjective: Nifedipine (NIFD), a calcium channel blocker with poor aqueous solubility and low oral bioavailability, requires formulation enhancement for effective delivery. This study aimed to develop and optimise a self-microemulsifying drug delivery system (SMEDDS) of NIFD and incorporate it into mouth-dissolving films (MDFs) to improve solubility, dissolution, and patient compliance.
Methods: Box-Behnken Design (BBD) was employed to optimise SMEDDS formulations using castor oil (A), Tween 80 (B), and Span 80 (C) as factors, with droplet size (Y1) and transmittance (%) as responses. The optimised SMEDDS batches (FS14-FS16) were characterised for droplet size, PDI, zeta potential, and transmittance and subsequently incorporated into MDFs (F1-F3) by solvent casting.
Results: The optimised SMEDDS exhibited droplet sizes between 196-201 nm, PDI values of 0.534-0.608, and zeta potentials from-15.66 to-21.07 mV, indicating nanoscale dispersion and moderate stability. The resulting SMEDDS-loaded films (F1-F3) showed uniform thickness (0.11-0.15 mm), rapid disintegration (48-60 s), and high drug content (87.04-95.08%). The diffusion of NIFD increased by a factor 3 after incorporating it into SMEDDS.
Conclusion: The optimised nifedipine-loaded SMEDDS (FS14-FS16) successfully incorporated into mouth-dissolving films (F1-F3), significantly enhanced solubility and dissolution. Among the MDFs, F1 emerged as the best, demonstrating superior in vitro drug release compared to the pure NIFD film, offering a promising oral delivery system for enhancing the bioavailability of poorly soluble drugs
ANTI-INFLAMMATORY AND ANTI-HEMORRHOIDAL ACTIVITY OF POLYHERBAL GEL WITH THEIR CHARACTERIZATION USING CROTON OIL-INDUCED MODEL AND IN SILICO ACTIVITY AGAINST INFLAMMATORY MEDIATORS
No full textABSTRACT
Objective: To formulate and optimize a polyherbal gel containing Azadirachta indica, Melia azedarach, Piper longum and Piper nigrum extracts and evaluate its anti-hemorrhoidal effect in rat model of croton oil-induced haemorrhoids and anti-diabetic effect by molecular docking.
Methods: Using fruit extracts, HPLC and HPTLC analysis were used to analyse phyto-chemicals (azadirachtin, gallic acid, quercetin, rutin, ellagic acid, etc.). The gels were prepared using mixture of plant extract and optimized for anti-inflammatory activity. Evans blue extravasation, recto-anal coefficient, TNF-α, IL-6, neutrophil count and histopathological examination in wistar rats was done for anti-haemorrhoidal activity. In Silico activity of the bioactive compounds were attached to the inflammation and metabolism-related proteins, that is COX-2, 5-LOX, MMP-9 and α-glucosidase.
Results: The extraction yield of A. indica fruits ranged from 1.6% to 4.8%, P. longum from 2.5% to 5.0%, P. nigrum from 2.1% to 4.4% and Melia azedarach was 5.1% in petroleum ether, 3.8% in chloroform, 3.4% in ethyl acetate and 5.3% in ethyl alcohol, with extraction times between 8 and 14 h. Among the solvents used, ethanol (95%) produced the highest extractive yield for all fruits. HPTLC of the combined mixture fraction showed peaks for rutin (Rf 0.16), gallic acid (Rf 0.47), quercetin (Rf 0.58), and ellagic acid (Rf 0.81), with additional peaks at Rf 0.34–0.38. Semi-quantitative analysis indicated rutin (2.8 mg/g), quercetin (2.5 mg/g), gallic acid (2.4 mg/g), and ellagic acid (1.3 mg/g). In the hemorrhoidal rat model, CMF (1:1:1:1) at 400 mg/kg reduced Evans blue to 0.38±0.02 µg/g, neutrophils to 16.5±0.6%, recto-anal coefficient to 0.91±0.01, serum TNF-α to 173.5±1.3 pg/ml, serum IL-6 to 91.2±0.6 pg/ml, protein TNF-α to 135.3±8.5 pg/mg, protein IL-6 to 248±12.0 pg/mg, and restored stool weight to 17.3±0.18 g. CMF (1:1:2:2) showed comparable reductions (Evans blue 0.37±0.02 µg/g; neutrophils 15.5±0.6%; recto-anal coefficient 0.89±0.01; serum TNF-α 166.8±1.2 pg/ml). Based on anti-hemorrhoidal activity CMF (1:1:1:1) and CMF (1:1:2:2) were selected for gel formulation. In the carrageenan-induced paw edema model, CMF-G1 (1111) reduced paw volume to 1.13±0.05 ml (2 h) and 0.95±0.04 ml (4 h), producing 48.2±0.31% edema inhibition, while CMF-G2 (1122) reduced paw volume to 1.20±0.02 ml (2 h) and 1.10±0.03 ml (4 h), with 35.4±0.42% inhibition, compared to 56.0±0.31% for diclofenac gel.
Conclusion: The herbal gels formulated were effective and synergistic, exhibiting biphasic anti-hemorrhoidal and strong α-glucosidase inhibitory activities suggesting development of a novel treatment for hemorrhoids with simultaneous metabolic dysfunctions which is phytotherapeutic, safe and effective
IN SILICO INVESTIGATION OF CONVOLVULUS PROSTRATUS AS A POTENTIAL SOURCE OF Α-GLUCOSIDASE INHIBITORS FOR DIABETIC MANAGEMENT
No full textObjective: Diabetes mellitus (DM) remains a major global health concern, and inhibition of intestinal α-glucosidase is a well-established therapeutic approach for managing postprandial hyperglycemia. Convolvulus prostrates (C. prostratus) contains several phytochemicals with reported antidiabetic relevance. This study aimed to computationally assess selected constituents from C. prostratus for their potential α-glucosidase interactions using an integrated in silico strategy.
Methods: Molecular docking, molecular mechanics–generalized born surface area binding free energy calculations, 100 ns molecular dynamics (MD) simulations, and absorption, distribution, metabolism, excretion, and toxicity predictions were performed to evaluate the interaction profiles and drug-likeness of prioritized phytoconstituents against human maltase–glucoamylase (PDB ID: 3TOP).
Results: Among the screened compounds, A18 (identified as quercetin, a well-known flavonoid previously reported in C. prostratus), showed comparatively favorable docking affinity (ΔG = −9.549 kcal/mol) and MM-GBSA binding energy (ΔG_bind = −31.44 kcal/mol) relative to the other constituents evaluated. MD simulations indicated that the quercetin–enzyme complex maintained stable binding, with consistent interactions involving key catalytic residues such as Asp1157, Asp1279, and Asp1526. ADMET profiling suggested good oral absorption and acceptable physicochemical characteristics, while noting that its predicted blood–brain barrier permeability may represent a potential liability for an intestinal enzyme inhibitor.
Conclusion: This study provides computational support for quercetin’s contributory role as one of the phytochemicals in C. prostratus capable of interacting with α-glucosidase. While quercetin demonstrated favorable in silico interaction and pharmacokinetic features compared with the other evaluated constituents, these findings primarily reinforce its known bioactivity and highlight the need for further in vitro and in vivo validation to substantiate its therapeutic relevance
EVALUATION OF SERUM LEVELS OF CYP2D6, CYP3A4, GSH, AND MDA AS PREDICTIVE BIOMARKERS FOR METHAMPHETAMINE-INDUCED LIVER DYSFUNCTION USING ADVANCED STATISTICAL MODELING
No full textObjective: This study aimed to evaluate the predictive potential of serum protein levels of CYP2D6, CYP3A4, glutathione (GSH), and malondialdehyde (MDA) as early biomarkers of METH-induced liver dysfunction using multivariate statistical approaches, compared to standard LFTs.
Methods: This case–control study included 90 METH users and 45 healthy control individuals. Serum CYP2D6, CYP3A4, GSH, and MDA levels, and routine LFTs were determined. Analysis was performed using principal component analysis (PCA), receiver operating characteristic (ROC) curves, and decision tree modeling.
Results: METH users showed significantly decreased serum levels of CYP2D6, CYP3A4, and GSH and higher MDA levels (p<0.0001), suggestive of oxidative metabolic disequilibrium. While most routine LFTs were normal, other markers, including AST, AST/ALT ratio, and albumin-to-globulin ratio, increased significantly. PCA demonstrated that early injury components could be divided into separate groups according to the markers of their metabolic and oxidative components. CYP2D6 ≤ 1.98 ng/ml was the best discriminating predictor according to the decision tree with 93.3% accuracy (AUC = 94).
Conclusion: Serum protein levels of CYP2D6, CYP3A4, GSH, and MDA demonstrated high sensitivity for detecting subclinical liver injury in METH users before conventional LFTs became abnormal. Their integration into diagnostic models may facilitate early interventions in high-risk populations
COMPUTATIONAL INSIGHTS INTO THE ALLOSTERIC INHIBITION OF BACE1 BY SULFORAPHANE: A MOLECULAR DOCKING AND DYNAMICS STUDY
No full textObjective: This study aimed to investigate the allosteric binding site and dynamic stability of the sulforaphane-BACE1 complex to provide structural insights into its selective inhibition mechanism.
Methods: Molecular docking was performed using YASARA Structure, followed by five independent 10 ns molecular dynamics simulations conducted with GROMACS to evaluate the stability of the sulforaphane–BACE1 complex. Key interactions and stability parameters were analyzed using RMSD-based metrics and interaction fingerprint profiling.
Results: Global docking identified 35 possible binding pockets, with one predominant allosteric site showing the most favorable binding energy and clustering. Molecular dynamics simulations revealed that sulforaphane maintained stable orientations in two of five trajectories (R2 and R4), indicating replica-dependent stability consistent with moderate affinity and allosteric flexibility. Interaction analysis highlighted persistent hydrophobic contacts with ALA173, LEU172, PRO313, GLU315, and ASP323 as major stabilizing residues.
Conclusion: Sulforaphane demonstrates moderate but reproducible allosteric binding to BACE1, primarily stabilized by hydrophobic interactions and key polar contacts. These findings establish a structural model supporting sulforaphane’s selective modulation of BACE1 and provide a computational framework for designing improved allosteric inhibitors for Alzheimer’s disease therapy
FORMULATION, CHARACTERIZATION AND PHARMACOKINETIC EVALUATION OF RIVAROXABAN-CITRIC ACID COCRYSTALS WITH ENHANCED SOLUBILITY, STABILITY AND BIOAVAILABILITY
No full textObjective: The attempt was made to improve solubility, flow properties, stability and bioavailability of rivaroxaban (RRB) by cocrystal formation.
Methods: The attempt was made to fabricate microwave assisted cocrystals of RRB using 10 different solid carboxylic acids as a cocrystal formers in 1:1 and 1:2 stoichiometric ratio. All the drug-coformer combinations were subjected to solubility analysis. Rivaroxaban-citric acid (RRB-CA)was further subjected to characterizations like Fourier transform infrared (FTIR), differential scanning colorimetry (DSC) and x-ray diffraction (XRD) to confirm the formation cocrystals as it shown highest solubility sediment delivery model (SeDeM) analysis was implemented to estimate comparative compressibility of pure drug and cocrystals. Cocrystals were further formulated into an immediate-release tablet and subjected to dissolution analysis in comparison with pure drug tablet. The comparative pharmacokinetic analysis was performed using wistar rats to. The comparative stability and shelf-life analysis was performed.
Results: Solubility analysis showed highest solubility with RRB-CA combination. The characterizations like FTIR, DSC and XRD confirmed the formation cocrystals. SeDeM (Sediment Delivery Model) analysis showed improved flowability and compressibility after cocrystal formation. The comparative dissolution study performed with pure RRB tablet and RRB-CA cocrystals showed improved dissolution after cocrystallizaion. The pure drug showed % drug release60.02±3.80% while RRB-CA cocrystals showed the drug release of 99.20±2.89%. Pharmacokinetic analysis performed using wistar rats demonstrated the improved bioavailability of RRB when administered as cocrystal. The pharmacokinetic parameters like peak plasma concentration (Cmax), AUC0-t(area under curve 0-t) and AUC0–∞(area under curve 0-∞)were significantly improved with cocrystallization. The peak plasma concentration of RRB pure drug was14.3389±1.4116µg/ml while for RRB-CA cocrystal it was 23.9644±1.5870 µg/ml. In shelf-life analysis, RRB showed the shelf life of 15.45 mo while cocrystal tablet showed the shelf life of 26.25 mo.
Conclusion: The cocrystallization of RRB with CA resulted in improved solubility by 5.80 folds while powdered dissolution showed the improvement by 1.65 folds. The results of kinetic study also demonstrated the improvement Cmax by 1.67 folds and AUC by 1.55 folds. Overall, the cocrystallization resulted in improved solubility, dissolution, bioavailability and stability
EVALUATING THE ANTI-INFLAMMATORY POTENTIAL OF GAMMA ORYZANOL FROM ORYZA SATIVA BY TARGETING THE NF-KB PATHWAY: A MOLECULAR DOCKING AND STRUCTURE-BASED PHARMACOPHORE MODELING APPROACH
No full textObjective: The nuclear factor kappa-B (NF-κB) pathway is a key regulator of inflammation observed in polycystic ovary syndrome (PCOS), rendering it a promising target for treatment. Gamma oryzanol (γ-oryzanol) has been reported to display anti-inflammatory properties. However, the particular γ-oryzanol compounds and their specific molecular mechanism by which γ-oryzanol interacts and modulates NF-κB activity have yet to be explained. The study intended to explore the molecular interactions underlying the anti-inflammatory activity of γ-oryzanol against NF-κB through in silico molecular docking and structure-based pharmacophore modeling.
Methods: A receptor-based pharmacophore model was created from the ligand-binding site of the NF-κB through the Molecular Operating Environment 2019 software. The pharmacophore comprised four features: one hydrogen bond donor, one hydrogen bond acceptor, one aromatic, and one hydrophobic feature. The optimized model was used to screen an in-house phytochemical database to find the hit compounds with matching features, followed by molecular docking of hit compounds to evaluate their binding manners and interactions with NF-κB. The docking poses were analyzed for key interactions and ranked based on their docking scores.
Results: Four lead compounds that satisfied the pharmacophore query were 24-methylenecycloartenyl ferulate, cycloartenyl ferulate, campesteryl ferulate, and β-sitosteryl ferulate. The docking results showed that 24-methylenecycloartenyl ferulate had the most potent interaction with NF-kB (-6.9 kcal/mol), followed by cycloartenyl ferulate (-6.7 kcal/mol), campesteryl ferulate (-5.9 kcal/mol), and β-sitosteryl ferulate (-5.1 kcal/mol), indicating their potential to modulate NF-κB.
Conclusion: The present study provides molecular insights into the potential modulatory mechanism of γ-oryzanol against NF-κB. γ-oryzanol, along with structurally related phytochemicals, may serve as a promising scaffold for targeting NF–κB–mediated inflammation, implicated in PCOS. These computational predictions offer a foundation for experimental validation in related inflammatory disease models
AN OBSERVATIONAL STUDY ON EMPIRICAL THERAPY IN ICU PATIENTS WITH SEPSIS IN A TERTIARY CARE HOSPITAL
No full textObjective: Sepsis is a life-threatening organ dysfunction caused by dysregulated host response to an infection. This study investigated antibiotic prescribing patterns, antimicrobial resistance, and their impact on prognosis and quality of life in critically ill patients with sepsis.
Methods: A prospective observational study was conducted at Srinivas Institute of Medical Science and Research Centre. For over six months, 174 ICU patients diagnosed with sepsis were assessed. Patient demographics, infection source, Sequential Organ Failure Assessment (SOFA) scores, antibiotic regimens, and clinical outcomes were collected.
Results: The study population was predominantly male (69.54%) with a mean age of 54 y. Piperacillin/Tazobactam (46.55%) and Meropenem (36.78%), both classified as WHO Watch antibiotics of AWaRe Classifications, were the most commonly prescribed antibiotics. This suggests a potential deviation from WHO guidelines and raises concerns about antibiotic resistance. Pseudomonas (15%) was the leading pathogen, exhibiting high resistance levels. While SOFA scores did not significantly differ between survivors and non-survivors, they correlated with length of stay, indicating disease severity. The SF-20 questionnaire revealed poor health perception and reduced social functioning across all age groups in surviving patients, impacting quality of life.
Conclusion: This study highlights a trend of over-prescription of broad-spectrum antibiotics, potentially deviating from WHO recommendations. The dominance of highly resistant g-negative bacteria underscores the need for targeted antibiotic selection based on local resistance patterns. SOFA scores reflected disease severity but did not predict mortality. The study emphasizes the lasting impact of sepsis on patients\u27 physical, social, and mental well-being, suggesting the importance of comprehensive post-discharge rehabilitation programs
ANTIMICROBIAL PRESCRIPTION PRACTICES AMONG THE INPATIENTS OF E. N. T DEPARTMENT USING WHO AWARE CLASSIFICATION: A CROSS-SECTIONAL STUDY
No full textObjective: To collect antimicrobial prescriptions of patients admitted to the E. N. T ward. To analyze the collected antimicrobial prescriptions of E. N. T inpatients based on the WHO AWaRe classification.
Methods: An observational cross-sectional study was conducted in the Department of E. N. T at a tertiary care hospital in Tirupati, Andhra Pradesh, from January to June 2025, after obtaining approval from the Institutional Ethics Committee. All inpatient prescriptions containing at least one antibiotic, irrespective of age, gender, or indication, were included. Written informed consent was obtained from adult participants, and assent from parents for minors. The original prescriptions were returned after documentation, and photocopies or photographs were analyzed. Antibiotics were classified according to the WHO AWaRe classification (2023), and WHO core prescribing indicators were applied to assess rational drug use.
Results: Out of 310 prescriptions analyzed, Amoxyclav (82.58%) from the Access group was most frequently prescribed, followed by Watch group antibiotics-Ceftriaxone (13.55%) and Cefixime (3.87%). No Reserve antibiotics were used. The average number of drugs per encounter was 5.13, and 100% of prescriptions contained antibiotics. Injections were used in 86.4%, 97% of drugs were from the Essential Medicine List, and 100% were prescribed by generic name.
Conclusion: The predominance of Access group antibiotics indicates partial adherence to WHO guidelines; however, polypharmacy and high antibiotic use highlight the need to strengthen antimicrobial stewardship in the E. N. T department
NANOPARTICLES USED FOR THE TREATMENT OF DIABETES
No full textThe worldwide health crisis caused by diabetes mellitus calls for novel therapeutic solutions because traditional treatments have shown their limitations. The review conducts an in-depth evaluation of nanoparticle-based technologies within diabetes care. For this, their functions in drug transport optimization and enhanced substance distribution, along with prolonged blood sugar stabilization capabilities, are examined and investigated. Different types of nanoparticle platforms, which include polymeric, lipid-based, inorganic, and natural nanoparticles, have shown excellent achievements in both preclinical research and clinical practice by delivering targeted drugs while minimizing adverse effects alongside glucose-triggered insulin release. The review explains how smart insulin delivery methods, along with anti-inflammatory care and personalized nanomedicine solutions, have progressed; however, it details the barriers that exist for biocompatibility and regulatory requirements and large-scale production. Laboratory research shows that nanotechnology has great potential for diabetes treatment through independent glucose control systems and simplified drug delivery processes, leading to better healthcare results. Nanoparticles offer promise to achieve disease modification rather than symptom management, even though their production requires solutions, and their long-term effects need further investigation. Nanomedical research should concentrate on maximizing smart nanoparticulate development while creating scalable manufacturing processes and developing patient-customized therapy models to establish nanomaterials fully in diabetes treatment practice