Journal of Applied Pharmaceutical Research (JOAPR)
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Role of intrinsic and supplemented antioxidants in follicular fluid: a shield against oxidative stress in oocyte health and embryo development
Get PDFBackground: In In Vitro Fertilization (IVF), a form of Assisted Reproductive Technologies (ART), the quality of oocytes and the successful development of embryos are crucial in determining the rate of fertility. The excessive presence of ROS (Reactive Oxygen Species) can cause oxidative stress, which negatively affects follicular fluid (FF) and oocyte maturation. Certain non-endogenous antioxidants, such as catalase, glutathione, and Superoxide Dismutase (SOD), are already present in Follicular fluid, which counterbalances these ROS and protects oocytes. Method: In addition to examining the possibility of exogenous supplements of antioxidants, such as vitamins C and E, and Coenzyme Q10 (CoQ10), this review investigates the function of these intrinsic antioxidants in maintaining oocyte health. Result: According to current in vivo and in vitro research findings done in mice, pigs, sheep, cows, and 18 patients in the age group(40±1), respectively, targeted antioxidant supplementation may enhance oocyte quality, embryo viability, and pregnancy outcomes. Conclusion: However, addressing individual heterogeneity in oxidative stress and optimizing dosage remains challenging. This review highlights how new antioxidant compounds and targeted interventions may enhance reproductive success by promoting cellular resilience in follicular fluid (FF). However, additional research into targeted antioxidant therapy in IVF is necessary
Innovative nanostructured lipid carrier gel for enhanced topical delivery of roflumilast in psoriasis management
Get PDFBackground: Psoriasis is a chronic immune-mediated skin disorder marked by keratinocyte hyperproliferation, inflammation, and oxidative stress, causing erythematous, scaly plaques that impair quality of life. Current therapies have side effects and poor solubility, highlighting the need for improved topical delivery systems. Methodology: An NLC-based gel encapsulating the PDE4 inhibitor roflumilast was developed for enhanced topical delivery. NLCs were prepared by high-pressure homogenization with oleic acid, glycerol monostearate, and Tween 80, and incorporated into a Carbopol 934 gel. The physicochemical properties, encapsulation efficiency, in vitro release, and in vivo efficacy of imiquimod in imiquimod-induced psoriatic rats were evaluated. Results: The developed gel was homogeneous, white, and transparent, with a dermally compatible pH (5.36-5.85), optimal viscosity (3.5-14.5 Pa·s), and good spreadability (4.3-7.2 g/cm/s). Formulation F3 showed high encapsulation efficiency (90.38 ± 2.91%) and sustained drug release (~90% over 24 hours). Drug content ranged from 72% to 95%. Ex vivo skin permeation studies demonstrated enhanced roflumilast penetration. In vivo application led to a significant reduction in psoriasis area and severity index (PASI) scores from 6.5 on Day 1 to 1.6 on Day 9. No signs of erythema, edema, or rashes were observed during the 72-hour skin irritation study, confirming excellent dermal compatibility. Histopathology confirmed decreased inflammation, reduced hyperkeratosis, and restored epidermal architecture. Discussion: The NLC-based roflumilast gel showed favorable physicochemical and biopharmaceutical properties, offering improved delivery and sustained release over conventional psoriasis therapies. Conclusion: Roflumilast-NLC gel is a promising topical therapy for psoriasis with controlled release and enhanced skin retention
In silico assessment of flavonoids from Matricaria chamomilla for anti-psoriatic potential via molecular docking and ADME/T profiling
Get PDFBackground: Computational tools are advancing in the drug discovery process to assess the safety profiles of new compounds with reduced investment. Herbal remedies exhibit a diverse range of active compounds that can alleviate various disease conditions with fewer side effects. Method: This study investigates the molecular docking of phytochemicals from Matricaria Chamomilla against inflammation-induced skin disorders, such as psoriasis. Using AutoDock Vina and MGL Tools, key compounds were evaluated for binding affinity with target proteins. ADMET analysis, as assessed by pkCSM and SWISSADME, to predict the Lipinski’s Rule of Five. Redocking was implemented to confirm the binding affinity of the docked position. Results: This molecular docking of phenolic compounds and flavonoids, including quercetin, apigenin, rutin, luteolin, and various glycosylated derivatives—from Matricaria Chamomilla against cellular proteins implicated in psoriasis (PDE-4, p38MAPK, IL-23, BTK, JAK-3, TNF-α, IL-17A, and IL-6). Using Autodock Vina and MGL Tools, rutin and quercetin demonstrated favourable binding affinities. At the same time, luteolin-7-glycoside exhibited the highest docking scores (e.g., -10.8 kcal/mol for PDE-4, -9.7 kcal/mol for JAK-3, and -9.1 kcal/mol for TNF-α) compared to the standard. Results highlight the potential of chamomile phytochemicals as safe, orally effective agents for managing inflammatory skin conditions. Redocking confirms the RMSD values are within the limits of < 2 A0. Conclusion: The data suggest that chamomile flavonoids could be safe and beneficial for treating inflammatory diseases and psoriasis. Although enzymatic and cell-based assays, along with further preclinical evaluations, are essential for advancing research in disease modification, formulation strategies play a role in improving drug characteristic
Investigation of potential efficacy of nanospanlastic vesicular drug delivery system for targeting the brain: formulation, characterization, and in-vivo studies
Get PDFBackground: Edaravone, a potent antioxidant, has limited brain bioavailability due to poor solubility and restricted permeability across the blood-brain barrier (BBB). Intranasal delivery offers a promising alternative for brain targeting by bypassing the BBB. Objective: To develop and evaluate a nanospanlastic-based in-situ nasal gel formulation of edaravone for enhanced brain delivery. Methodology: A Quality by Design (QbD) approach was employed to identify and optimize critical formulation variables using Plackett-Burman and Central Composite Design. The optimized nanospanlastics were incorporated into a gellan gum-based ion-activated in-situ nasal gel and characterized through in vitro, ex vivo, and in vivo studies. Results and Discussion: The optimized formulation exhibited a particle size of 213.4 nm, a drug entrapment efficiency of 67.59%, and rapid gelation upon contact with nasal fluid. In vitro diffusion showed over 80% drug release within 30 minutes, while ex vivo studies confirmed improved permeation (flux: 7.8067 µg/cm²/hr). Histopathology revealed no nasal mucosal irritation. Pharmacokinetic studies in rats demonstrated significantly enhanced brain and plasma exposure compared to the marketed edaravone injection, with higher Cmax (78.73 ng/mL), Tmax (121.2 min), and AUC. Conclusion: The developed nanospanlastic-based nasal gel offers a non-invasive, effective strategy for brain delivery of edaravone, with potential to improve therapeutic outcomes in neurological disorders
Design and optimization of chitosan microspheres loaded with green tea phytosomes for sustained release
Get PDFBackground: Phytosomes are nanovesicular systems that integrate plant extracts with phospholipids to improve the solubility, stability, and bioavailability of phytoconstituents. Green tea (Camellia sinensis) is rich in polyphenols such as epigallocatechin gallate (EGCG) and epigallocatechin (EGC), which possess significant therapeutic potential but are limited by poor absorption and stability. The present study aimed to formulate and evaluate green tea extract–loaded phytosome-incorporated microspheres with desirable physicochemical characteristics for sustained delivery. Methodology: Phytosomes were prepared using the thin-layer hydration method with varying molar ratios (0.5–1.0) of phospholipids to standardized green tea extract (sample 1 and sample 2). The optimized phytosomes were further encapsulated into microspheres via emulsion cross-linking, employing different concentrations of glutaraldehyde and polymer to obtain nine formulations. Design Expert software was applied for optimization, and the microspheres were evaluated for micrometric properties, entrapment efficiency, drug loading, drug release, swelling behaviour, mucoadhesion, stability, and surface morphology. Results and Discussion: The prepared microspheres exhibited a spherical morphology with satisfactory physicochemical properties. Among the formulations, batch F3 of sample 1 demonstrated the most promising results, achieving 87% yield, 77% drug entrapment efficiency, 30% drug loading, and 91.87% cumulative drug release up to 9 hours, along with favorable swelling and mucoadhesion properties. Stability studies further confirmed the reliability of the formulation. Conclusion: Overall, the developed phytosome-loaded microspheres of green tea extract exhibited an improved release profile, stability, and potential fwr sustained drug delivery, suggesting their applicability in enhancing the therapeutic efficacy of green tea polyphenols
pH independent controlled release of verapamil hydrochloride using HPMC-alginate matrices & organic acids
Get PDFBackground: Verapamil HCl, a weakly basic drug, exhibits pH-dependent solubility that limits sustained-release formulation efficacy. This study developed controlled-release matrix tablets using HPMC, sodium alginate, and organic acids to achieve pH-independent drug release. Methodology: Sixteen formulations (F1-F16) were prepared using a 2⁴ factorial design with varying concentrations of organic acids (citric/fumaric: 50-75 mg), sodium alginate (50-80 mg), and HPMC K4M (30-50 mg). Evaluations included pre- and post-compression studies, dissolution testing under a two-stage pH protocol (pH 1.2 for 2 hours, then pH 6.8 for 10 hours), microenvironmental pH monitoring, and kinetic modeling. Results and Discussion: All formulations met pharmaceutical standards, with hardness of 6.88-7.55 kg/cm², friability <0.55%, and drug content of 98.65-99.68%. Fumaric acid formulation F8 achieved superior performance with 89% drug release and the highest pH-independence (f₂ = 91.2) compared to control F1 (72% release, f₂ = 85.3). Microenvironmental pH monitoring revealed that F8 maintained sustained acidification (pH 4.10-4.75) for 12 hours, whereas citric acid formulations showed premature acid depletion. All formulations fitted the Korsmeyer-Peppas model (R² > 0.99), with F8 exhibiting diffusion-controlled release (n = 0.512). Statistical optimization identified fumaric acid as the most significant factor (F-value = 26.30, p = 0.0003). Conclusion: Incorporating 75 mg fumaric acid in HPMC-alginate matrices provides robust, pH-independent sustained release through maintained microenvironmental acidification, offering a validated solution for weakly basic drugs in sustained-release formulations
Thermal sintering driven modulation of drug release and buoyancy characteristics in dasatinib gastro-retentive tablets
Get PDFBackground: Thermal sintering is emerging as an innovative and cost-effective technique in pharmaceutical formulation design, especially for controlling drug release in oral dosage forms. This study investigates its applicability in the development of gastro-retentive floating tablets for Dasatinib, a tyrosine kinase inhibitor with low solubility and bioavailability. Methodology: Floating matrix tablets were developed via direct compression, incorporating carnauba wax and hydroxypropyl methylcellulose as matrix-forming agents, along with sodium bicarbonate as a gas-generating component to impart buoyancy. The tablets were then thermal-sintered at two temperatures for varying durations in a controlled hot-air oven. The effects of thermal sintering conditions were investigated with respect to in vitro dissolution, mechanical strength, percent water uptake, percent erosion, total buoyancy duration, floating lag time, and SEM morphology. Results and Discussion: Statistical analysis using two-way ANOVA (α = 0.05) revealed that sintering condition significantly influenced drug release and buoyancy performance (p < 0.01). Formulation DST 02 sintered at 70°C-3 hours exhibited optimal performance, achieving a maximum drug release of 96.3% over 13 hours. Characterization technique methods such as FTIR and DSC have confirmed the absence of chemical interactions and polymorphic transitions. Stability studies conducted in accordance with ICH guidelines indicated that the optimized formulation remained stable throughout the study period. Conclusion: Thermal sintering effectively modulated the release characteristics of Dasatinib from floating tablets, thereby increasing gastric retention time and facilitating sustained drug release. This technique holds promise for improving therapeutic efficacy, reducing dosing frequency, and enhancing patient compliance in oral drug delivery
Ameliorative potential of coumaric acid and imeglimin against reserpine-induced parkinsonism in rats
Get PDFBackground: Parkinson’s disease involves dopaminergic degeneration, oxidative stress, and α-synuclein aggregation. Reserpine-induced Parkinsonism mimics these deficits via VMAT-2 inhibition. Coumaric acid and imeglimin possess antioxidant and mitochondrial-protective actions. This study evaluated the individual and combined efficacy of these agents in reducing reserpine-induced behavioural and neurochemical impairments in rats. Methodology: PD was induced in rats by giving reserpine (1 mg/kg, s.c) alternately for three days. Pretreatment with coumaric acid (80 and 100 mg/kg, p.o.), imeglimin (100 & 200 mg/kg, p.o.), and their combination were administered for 5 days. Behavioral assessments (orofacial dyskinesia, H & B test, and rotarod) were performed on day 5, followed by biochemical oxidative stress parameters (CAT, GSH, SOD, and LPO), neurotransmitters (dopamine), and α-synuclein expression with histopathological evaluations. Results: Reserpine-treated rats exhibited pronounced orofacial dyskinesia, reduced motor coordination, dopamine depletion, elevated oxidative stress, and α-synuclein expression. Pretreatment with coumaric acid and imeglimin improved behavioral outcomes, restored antioxidant enzymes, reduced inflammation, and elevated dopamine levels. Combination therapy produced the greatest improvement. Discussion: The combined effects of coumaric acid and imeglimin likely counteract reserpine-induced dopaminergic toxicity through antioxidant enhancement and inhibition of α-synuclein expression. Conclusion: Coumaric acid and imeglimin combination therapy significantly mitigates reserpine-induced Parkinsonism by improving general neuronal integrity and brain function
Exploring the structural aspects of alanine racemase enzyme for antitubercular drug discovery – a computational approach
Get PDFBackground: Tuberculosis (TB) is a communicable disease that is a significant cause of ill health and one of the leading causes of death worldwide. The current antibiotics have been pivotal in managing TB to a greater extent. Still, the issue of antitubercular drug resistance is indeed a matter of concern and requires effective drug discovery strategies targeting less explored targets. One of the less explored but promising antitubercular targets, Alanine racemase (AlaR), a prokaryotic enzyme providing the essential peptidoglycan precursor D-alanine (D-Ala) in bacterial cell wall synthesis, is an attractive target for antitubercular drug discovery. Objective: The current study aims to explore the available protein targets of the AlaR enzyme in Mycobacterium tuberculosis and to understand the structural aspects to be followed in designing inhibitors for them. Methodology: As a part of the study, the crystal structure of the alanine racemase enzyme from Mycobacterium tuberculosis was subjected to computational studies using the Schrodinger drug design suite. The significant protocols followed involved protein preparation and fragment-based drug design studies. Results and discussion: The in-silico data suggested that substituted pteridine derivatives, which impart stable interaction at the active site of the alanine racemase enzyme, may be the potential lead moiety for drug design. Conclusion: Although the preliminary screening suggests that the pteridine ring system may be a promising lead, detailed in silico studies must be carried out, such as molecular mechanic generalized born surface area (MM-GBSA), density functional theory (DFT) studies, induced fit docking, molecular dynamics, etc. for further authentication. For effective correlation, detailed in vivo studies on AlaR enzyme inhibition can be carried out from a future perspective
Advancements in formulations and technologies for colon-targeted drug delivery
Get PDFBackground: Colonic administration of drugs may enhance drug absorption, reduce adverse reactions, and facilitate delivery to specific therapeutic targets. Objective: Delivering pharmaceuticals to the colon poses challenges that require innovative formulation strategies. Methodology: Various formulation approaches have been explored for colon-targeted drug delivery systems. These approaches target the colon using formulation components that interact with GI physiology parameters such as pH, colonic flora, and enzymes. Result and Discussion: The article discussed the various research studies conducted for colon targeting involving novel strategies such as pH-dependent, enzyme-dependent, Ligand-Receptor-based, new technologies, Phloral, and magnetically derived approaches. It also explored the translational technologies, such as in vivo, in vitro, and in silico, which expedite the transition from fundamental research to clinical application and enhance therapeutic outcomes. Conclusion: In conclusion, the most relevant preclinical studies, encompassing in vitro, in vivo, and in silico research, are delineated to facilitate the strategic advancement of novel colon-targeted therapeutics