Objective: This project aims to develop and evaluate solid lipid nanoparticles (SLNs) of an antiviral drug to improve bioavailability, reduce dosing frequency, and enhance patient compliance. SLNs offer a nanocarrier system that addresses the poor solubility, low oral bioavailability, and systemic side effects associated with conventional antiretroviral therapy. Methods: SLNs of dolutegravir were prepared using high shear homogenization followed by ultrasonication. Biocompatible lipids such as glyceryl monostearate were used as the lipid matrix, and Poloxamer 188 served as the stabilizer. To optimize the formulation, lipid content, surfactant type, concentration, and sonication parameters were systematically varied. The prepared formulations were evaluated for particle size, zeta potential, drug entrapment efficiency, and in-vitro drug release profile to determine the optimum conditions for SLN development. Results: The optimized solid lipid nanoparticle (SLN) formulation exhibited a particle size in the range of 257–412 nm with a negative zeta potential (ZP), indicating good physical stability and low aggregation tendency. A high drug entrapment efficiency (%EE) (>85%) confirmed effective incorporation of the drug within the lipid matrix. In vitro release studies demonstrated a biphasic release pattern, characterized by an initial burst release followed by sustained drug release over 24 hours. Differential Scanning Colorimetry (DSC) and Fourier Trasform Infrared Spectrocopy (FTIR) analyses revealed no significant drug–lipid interactions, confirming formulation compatibility. Transmission Electron Microscopy (TEM) analysis showed spherical nanoparticles with smooth surfaces and uniform morphology. Overall, the formulation displayed desirable physicochemical and release characteristics suitable for sustained drug delivery. Conclusion: The study demonstrates that solid lipid nanoparticles (SLNs) are a promising delivery system for antiretroviral drugs, offering sustained release, improved pharmacokinetic behavior, and reduced dosing frequency. However, further in vivo studies are required to confirm their therapeutic efficacy and biodistribution profile.
Objective: A robust and reliable analytical method for the quantification of dasatinib (DSB) is required for the design of such lipid nanoparticle (LNP) systems, as excipients may interfere and the drug may be unstable during analysis. Methods: A Quality by Design (QbD) approach was employed in the development and optimization of a reversed-phase high-performance liquid chromatography (RP-HPLC) method using a box-behnken design (BBD) to explore the relationships between the important variables in the chromatographic process. The optimized method was validated as per ICH guidelines, and it was found to be linear in the range of 50 to 5000 ng/ml with a good concentration-response relationship. Results: The method demonstrated excellent sensitivity, with limits of detection and limits of quantitation of 3.16 ng/ml and 9.56 ng/ml, respectively. Precision testing showed the method had good repeatability and percentage relative standard deviation (%RSD) within acceptable ranges. The method also demonstrated specificity via photodiode array detector (PDA) peak purity analysis, which yielded a purity index of 0.999, indicating no interference from excipients or degradation products. Forced degradation testing Experiments provided evidence that DSB was exhibited 13.91% degradation under acidic conditions (0.1 N HCl, room temperature (RT)) and 13.42% degradation under alkaline conditions (0.1 N NaOH, RT) and that the separation of intact Drug from Degradation Products supported the method's ability as a stability-indicating method on the dasatinib lipid nanoparticles (DSB-LNPs), with a 97.43% of percentage encapsulation efficiency (%EE), 3.98% of percentage drug loading (%DL), supporting its use in routine analysis. Conclusion: The validated QbD approach-based RP-HPLC method is robust, sensitive, and stability-indicating; therefore, it is the best choice for routine analysis of DSB in Bulk and LNPs.
Neurological disorders pose an unparalleled global health challenge, impacting over 3.4 billion individuals worldwide and serving as the primary cause of disability globally. This thorough review looks at synthetic exosomes as groundbreaking drug delivery systems. These delivery vehicles have been specially designed to cross the blood-brain barrier for use in the brain. The review examines various methods for loading cargo, including passive incubation for small molecules that are incompatible with water, electroporation for compounds and nucleic acids that are compatible with water, sonication techniques, pH gradient trapping, and more advanced approaches such as EXPLOR optogenetic systems Here, we examines various types of therapeutic cargo, including small molecules, proteins, peptides, RNA therapeutics (such as siRNA, miRNA,and antisense-oligonucleotides), mRNA, and the CRISPR/Cas9 gene editing system. It looks at the most up-to-date ways to improve things, such as combining nanotechnology with gold and iron-oxide nanoparticles for theranostic uses, using artificial intelligence to improve design, and using advanced imaging methods to track biodistribution in real time. Also, this review impact provides a crucial framework for understanding synthetic exosome technology's potential to revolutionize neurological therapeutics by solving the fundamental BBB delivery problem. The comprehensive analysis of loading methods, cargo types, and enhancement strategies offers researchers and clinicians essential insights for developing next-generation neurotherapeutics, potentially transforming treatment outcomes for billions affected by neurological disorders worldwide.
Objective: The present study aimed to develop and validate a simple, efficient, and robust analytical quality by design (AQbD) driven stability-indicating high-performance liquid chromatography (HPLC) method for the quantification of vonoprazan fumarate(VPF) in its pharmaceutical dosage form. Methods: An AQbD framework in conjunction with a Box-Behnken design was used to construct and optimize a stability-indicating HPLC technique. Retention time(RT) and tailing factor were used as response factors to evaluate method performance, whereas acetonitrile(ACN) concentration, flow rate, and column temperature were identified as essential method variables based on preliminary experiments. Forced degradation of VPF under International Council for Harmonisation (ICH) recommended stress settings verified specificity. The optimized approach was validated in accordance with ICH Q2 (R1). Results: Using a mobile phase of acetonitrile: 0.1% glacial acetic acid (pH adjusted to 6.5), (80: 20% v/v), chromatographic separation was accomplished on a Shimadzu C18 (250 mm × 4.6 mm, 5.0 µm) column. A photodiode array (PDA) detector was used to measure the separation at 230 nm. The method's capacity to indicate stability was demonstrated through forced deterioration trials. Under circumstances of oxidative, basic, and acidic stress, VPF degraded, but it remained resistant to photolytic and thermal degradation. Precision (%RSD<2), accuracy (98.34-98.83 %), robustness (%RSD < 1.1 for column temperature and wavelength), and sensitivity with low detection and quantitation limit values were all demonstrated during method validation. Conclusion: Implementation of AQbD driven systematic and risk-based approach into the development of a stability-indicating HPLC method for VPF enhanced method robustness, specificity and life cycle control.
Objective: To develop and optimize a silk fibroin–based composite film incorporating polyvinyl alcohol (PVA), hydroxyethyl cellulose (HEC), hyaluronic acid, and doxycycline, and to evaluate its antibacterial activity for potential in-vitro wound dressing applications. Methods: Films were prepared using varying concentrations of silk fibroin, PVA, and HEC. A 2³ factorial design was employed to evaluate the individual and interactive effects of silk fibroin (A), PVA (B), and HEC (C) on in-vitro drug release and drug content. The optimized formulation was subjected to physicochemical characterization, including thickness, surface pH, folding endurance, drug content uniformity, and bio-adhesion strength. In-vitro antibacterial activity evaluated against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa. Stability studies were conducted over a period of two months. Results: Drug release from the formulations ranged from 79.6% to 96.41%, while drug content varied between 85 and 98 mg. PVA significantly enhanced drug release (p = 0.0482), whereas the A×C interaction significantly influenced drug loading (p = 0.0282). The optimized formulation (NS18), containing 0.10 g silk fibroin, 1 g PVA, and 0.05 g HEC, showed 87.16% drug release and 93.12 mg drug content. Films exhibited uniform thickness (0.21–0.26 mm), skin-compatible pH (6.3–6.7), high folding endurance (265–305 folds), strong bio-adhesion (26.9–32.5 g), and pronounced antibacterial activity. Stability studies confirmed minimal changes in drug content and release. Conclusion: The optimized silk fibroin composite film demonstrated controlled drug release, favourable mechanical and bio-adhesive properties, and effective antimicrobial activity under in-vitro conditions, indicating its potential suitability as a biomaterial for in-vitro wound dressing applications. Further in-vivo and clinical investigations are required to establish its therapeutic efficacy.
Objective: The goal of this work is to create pyrimidin-phenoxy acetamide derivatives that effectively block Decoy Receptor 3 (DcR3). In-silico experiments such as molecular docking, molecular Mechanics generalized born surface area (MMGBSA) and absorption, distribution, metabolism and excretion (ADME) will be used to evaluate their efficacy. Methods: The Schrodinger sitemap discovered an active DcR3 site. XP-docking is used to test ligand binding affinity. The binding free energy and associated energy components were estimated through MM-GBSA analysis, and pharmacokinetic (ADME) properties were predicted using QikProp. Results: Compounds 3 (amino-pyrimidin-phenoxy acetamide) and 6 (chloro-pyrimidine-phenoxy acetamide) had attractive docking scores (-5.05 and -5.04 kcal/mol) and strong MM-GBSA binding free energies (-79.63 and -77.10 kcal/mol). They exhibit stability when TyrB:84, Ser A:120 and Asp A:119 residues are complexed by Vander Waals. Coulomb, lipophilic, hydrogen bonds and pi-pi interactions. Low toxicity (LD50=3000 mg/kg), high oral bioavailability, minimal CNS penetration and low cardiotoxicity were identified in ADME.Conclusion: These compounds show potential for further investigation as DcR3-targeting candidates for lung cancer. These ligands prevent sequestration and restore apoptosis, with a favourable binding profile, drug-like ADME characteristics and safe toxicity. Consider all of these factors and take the research to the next level such as in vivo validation.
This review aims to synthesize and evaluate current evidence on the role of eosinophils in the development of allergic diseases, the mechanisms of their activation and involvement in pathological processes, as well as modern therapeutic approaches aimed at modulating eosinophilic activity. The analysis indicates that elevated eosinophil levels in peripheral blood, sputum, and affected tissues are consistently associated with greater disease severity in bronchial asthma, allergic rhinitis, and atopic dermatitis. Across multiple observational studies and meta-analyses, patients with blood eosinophil counts >300 cells/µL demonstrated a higher risk of frequent asthma exacerbations, with odds ratios ranging from 2.9 to 3.4 across individual studies (95% CI not consistently reported). In addition, increased eosinophil accumulation in the bronchi has been associated with impaired pulmonary function, as reflected by a strong inverse correlation between sputum eosinophil levels and forced expiratory volume in one second (r = −0.92, p < 0.001). Evaluation of therapeutic evidence demonstrates that targeted monoclonal antibody therapies significantly reduce eosinophilic inflammation and improve clinical outcomes. Treatment with mepolizumab and benralizumab has been shown to reduce the annual frequency of asthma exacerbations from 3.7 to 0.7 cases (95% CI not consistently reported across trials) and decrease the average daily dose of oral corticosteroids by 8.7 mg. Furthermore, pooled analyses of randomized controlled trials indicate that tezepelumab reduces exacerbation rates by approximately 71% (pooled estimate, 95% CI not uniformly available across included studies), underscoring the relevance of upstream type 2 cytokine blockade in controlling allergic inflammation. Overall, the reviewed evidence confirms that eosinophil counts represent informative diagnostic and stratification biomarkers that support the implementation of personalised therapeutic strategies. However, substantial heterogeneity across studies limits direct comparability of effect sizes, emphasising the need for further research into eosinophil functional subtypes, context-dependent activation mechanisms, and long-term consequences of sustained eosinophil-targeted therapy. Such efforts are essential for improving disease prediction, refining patient selection, and guiding the development of next-generation therapeutic agents for allergic diseases.
Objectives: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterised by memory loss and cognitive decline. Glycogen Synthase Kinase-3β (GSK-3β) regulates tau phosphorylation, making it a promising therapeutic target. To the best of our knowledge, N-(anthracene-1-yl)-2-phenoxyacetamide analogues have not been reported as GSK-3β inhibitors. This study aimed to design and evaluate a novel series of these analogues as potential GSK-3β inhibitors using computational approaches. Methods: Ten ligands were designed and docked using Glide XP against GSK-3β (PDB ID: 1J1C). Binding stability was assessed through molecular mechanics-generalised born surface area (MM-GBSA) free energy calculations. Absorption, distribution, metabolism and excretion (ADMET) profiling (drug-likeness, toxicity) and protein-ligand interaction analysis were also performed. Results: Compounds 2(N-(anthracen-1-yl)-2-(4-hydroxyphenoxy)acetamide) and compound 3(2-(4-aminophenoxy)-N-(anthracen-1-yl)acetamide) showed docking scores (-5.45 and -5.79 kcal/mol) comparable to or better than the co-crystallised ligand (-5.40 kcal/mol). Since no approved drug directly targets GSK-3β, Donepezil (an FDA-approved acetylcholinesterase inhibitor for AD) was included as a reference comparator, against which both compounds performed better (-3.63 kcal/mol). MM-GBSA confirmed favorable binding free energies (-65.81 and -67.21 kcal/mol). ADMET predictions indicated Lipinski compliance, good oral absorption, CNS penetration and low toxicity. Interaction analysis revealed stable hydrogen bonding with Lys85 and Asn186, two critical residues of the GSK-3β catalytic site. Conclusion: Based on this computational analysis, compounds 2 and 3 demonstrated favourable pharmacokinetic features, significant binding affinity and binding stability. These scaffolds are therefore seen to be potential as GSK-3β targeting anti-Alzheimer's drugs. These chemicals require more in vitro and in vivo research.
Objective: This study aimed to develop and validate a Reverse-Phase High-Performance Liquid Chromatography (RP-HPLC) method for the simultaneous quantification of Selegiline and Brahmi (Bacopa monnieri) extract. Methods: The chromatographic method was optimized using the Quality by Design approach. Initially, risk assessment was carried out. From this, plausible factors were selected and screened using a screening design. Following this, the critical variables were optimized, and the design space thus obtained was verified using Monte Carlo Simulations. Chromatographic separation was achieved using a C-18 column with a mobile phase consisting of acetonitrile and 0.72% anhydrous sodium sulphate (31.5:68.5 v/v) at a flow rate of 1 mL/min, with detection wavelength optimised at 205 nm. The method was validated in accordance with ICH Q2(R2) guidelines, assessing linearity, accuracy, precision, limit of detection, and limit of quantification. Results: The developed method was linear over the concentration ranges of 2-10 μg/mL for Selegiline and 5-25 μg/mL for brahmi extract (BE). The method demonstrated excellent linearity for both drugs, with R values exceeding 0.99. Accuracy and precision values fell within acceptable ranges, indicating strong repeatability. In the system suitability test, the theoretical plates were found to be greater than 2000, and the tailing factor was less than 2. LOD and LOQ for Selegiline and BE were 0.86, 2.35, 0.71, and 2.35 μg/mL, respectively. The method was evaluated for its environmental impact using its green score. Conclusion: The validated RP-HPLC method was robust and reliable for the simultaneous quantification of Selegiline and Brahmi extract, making it suitable for quality control applications in pharmaceutical formulations.
Objective: The main aim of this study was to develop and evaluatea quality-by-design (QbD) optimized gastroretentive nanoparticle-based triple therapy comprising levofloxacin hemihydrate-loaded mucoadhesive nanoparticles (LMNP), amoxicillin-loaded nanoparticles (AMXNP), and esomeprazole (ESO), and to compare itsin vivo efficacyagainst conventional triple therapy for Helicobacter pylori (H.pylori) eradication. Methods: LMNP were formulated by ionic gelation using chitosan, carbopol 974P, and N-acetylcysteine (NAC), and optimized using a central composite design (CCD). AMXNP were prepared using a chitosan-alginate polyelectrolyte complex method. The nanoparticles were characterized for physicochemical properties, in vitro release, mucoadhesion, and mucopenetration. In vivo anti-H.pylori efficacy was evaluated in Swiss albino mice and compared with standard and conventional triple therapies. Results: Optimized LMNP showed a particle size of 251.70 ± 3.06 nm, an entrapment efficiency (EE%) of 65.84 ± 0.14%, a cumulative drug release (CDR) time of 4.66 ± 0.29 h (~5 h), and a mucoadhesive strength (MS%) of 65.12 ± 0.63%. AMXNP showed a particle size of 641.7 ± 3.22 nm and an EE% of 61.33 ± 4.16%. The nanoparticle-based triple therapy significantly reduced gastric H. pylori load to 6.30 × 10⁶ CFU/gastric wall (6.79 ± 1.41 log₁₀ CFU). It achieved clearance rates of 85.9% and 83.33%, which were markedly superior (***P < 0.001) to those of conventional H. pylori triple therapy (64.6% inhibition; 50% clearance). Histopathology confirmed reduced inflammation and near-normal gastric integrity in nanoparticle-treated groups. Conclusion: The QbD-CCD-optimized gastroretentive nanoparticle-based triple therapy achieved superior H. pylori eradication, gastric retention, and mucosal recovery compared with conventional therapy, indicating strong potential for effective and patient-compliant treatment.
Objective: The objectiveof the present study was to improve the solubility and dissolution rate of poorly water-soluble drug rosuvastatin (RSV). Methods: Solid dispersions were prepared by using Poly vinyl pyrrolidone K30 (PVPK30) and Aerosil 200 by spray drying method, with different drug: polymer ratio. These formulations were characterized for saturation solubility, infra-red spectroscopy (IR), differential scanning calorimetry (DSC), powder x-ray diffraction (PXRD) and scanning electron microscopy (SEM). Results: Saturation solubility of pure drug is 1.42±0.07.The aqueous solubility of RSV was favored by the presence of polymer PVPK30. Saturation solubility of SP4 formulation was found to be 89.5µg/ml which is increased compared to the pure drug. This could be due to increased wettability. In contrast to the very slow dissolution rate of pure RSV, spray dried solid dispersions considerably improved the dissolution rate. The dissolution rate of pure RSV is very low that is 24.03±1.7%drug is dissolved in 3 hours. Whereas all Solid dispersions of RSV with PVPK30(SP1 to SP4) significantly enhanced the dissolution rate of RSV. SP4 presented highest drug release 92.93±3.35%. The solid dispersions have increased the dissolution rate by the possible factors like 1) the strong hydrophilic characteristic of PVPK30 that improves the water penetration and the wettability of the hydrophobic RSV and 2) embedded drug particles in polymer bed, which results in absence of crystallinity. These results are confirmed by PXRD, DSC and SEM. IR studies revealed that there is hydrogen bonding formation between RSV and PVPK30. Conclusion: Solid dispersions of RSV prepared by the spray drying method shows significant potential for enhancing the solubility and bioavailability.
Objective: This study aims to isolate and characterise cellulose-rich fibres in four cultivars of avocado (Persea americana). There were four varieties, hass, bacon, maluma, and zutano, which determine the physicochemical properties that are relevant to their future use. Methods: The manual extraction protocol-based procedure has used a sieve system to isolate the fibres. In the context of a protocol, the naturally ripened avocado pulp has been extracted from four varieties of avocados, which is then subjected to a series of analytical methods that include fourier transform infrared spectroscopy, thermogravimetric analysis, coupled with field-emission scanning electron microscopy, coupled with energy-dispersive X-ray spectroscopy, and x-ray diffraction. Results: FTIR analysis confirms the presence of characteristics related to cellulose functional groups, including hydroxyl, aliphatic C-H, and glycosidic linkages. The FESEM imaging revealed cultivars compact fibrillar structures, while maluma and zutano exhibited more irregular and porous surfaces. TGA demonstrated differences in thermal stability among cultivars, with bacon fibers exhibiting the highest degradation temperature (367 ± 4 °C), followed by Hass (359 ± 3 °C). XRD analysis future indicated variation in crystallinity index, ranging from approximately 61% in bacon to 49% in maluma. Conclusion: This study provides a material-level picture and understanding of fundamental characterisation that proves the value of avocado-derived cellulose fibres to have physicochemical attributes that can be used in future applications.
Objective: Mangosteen rind (Garcinia mangostana L) is a plant that is quite popular in Indonesia. Mangosteen rind extract contains alpha-mangostin. Poor water solubility of alpha mangostin limits its oral bioavailability. The formulation in the form of SNEDDS is expected to increase the solubility and bioavailability of the active fraction of mangosteen rind. Dichloromethane (dcm) fraction has high antioxidant activity so it is used as an active substance in SNEDDS formulation. To optimize a self-nanoemulsifying drug delivery system (SNEDDS) to enhance solubility, dissolution, and oral delivery of alpha mangostin. Methods: Solubility screening was performed in various oils, surfactants, and co-surfactants. The optimized SNEDDS was evaluated for droplet size, PDI, zeta potential, and stability under centrifugation, heating–cooling, and freeze–thaw cycles. Dissolution studies were conducted in vitro, and cumulative release profiles were analyzed kinetically. Results: The optimized SNEDDS (1.64:7.34:1.02, isopropyl myristate: Tween 20: propylene glycol) formed nanoemulsions with droplet size 50.6±1.37 nm, PDI 0.206±0.0036, and zeta potential-15.35±0.81 mV. Stability tests showed no significant change after stress conditions. Transmittance was 70.125%, indicating adequate clarity. Dissolution was significantly improved compared to dcm fraction. The R2 calculation results obtained for the zero-order data were 0.5882, first-order 0.8852, Higuchi 0.6945 and Korsmeyer-Peppas 0.8556. Therefore, it can be concluded that the release kinetics for the dcm fraction of SNEDDS follows a first-order model, with the R2 value approaching 1. This means that the drug release rate is directly proportional to, or dependent on, the remaining drug concentration in the dosage matrix. Conclusion: Optimized SNEDDS improved dissolution and demonstrated robust physical stability under stress conditions, highlighting its potential for oral delivery of α-mangostin.
Vincristine (VCR) remains a cornerstone of oncological therapy. Yet, its efficacy against central nervous system (CNS) malignancies is severely hindered by the blood-brain barrier (BBB) and dose-limiting peripheral neurotoxicity. This comprehensive review explores the promising shift from conventional systemic administration to advanced nanovesicular platforms designed for direct nose-to-brain (N2B) delivery. We evaluate the comparative performance of diverse carriers, including nanoemulsions, niosomes, liposomes, and nanostructured lipid carriers (NLCs). Central to this review is the analysis of strategic excipient chemistry, specifically the synergistic interplay between chitosan for mucoadhesion and tight-junction modulation, Tween 80 for P-glycoprotein (P-gp) efflux inhibition, and PEG 6000 for mucus penetration, as well as the impact of Soluplus® integration in nanovesicular engineering. We also provide an assessment approach using quantitative brain-targeting indices, including drug targeting efficiency (DTE%) and direct transport percentage (DTP%), which are essential for brain-targeting evaluation. We also highlight the critical role of scintigraphic validation using 99mTc-labeled formulations in providing spatial proof of the olfactory and trigeminal bypass routes. Safety considerations, particularly ciliary beat frequency (CBF) and histopathological integrity, are discussed to establish a framework for clinical translation. Ultimately, this review consolidates evidence that multifunctional nanovesicles offer a sophisticated route of entry into the CNS, optimizing therapeutic indices for VCR as a CNS drug model while mitigating systemic risks.
For more than a decade, transdermal nanoemulsions (NEs) have shown potential in overcoming the barrier properties of the skin and enhancing the percutaneous absorption of many drugs. In the last few years, great attention has been focused on the design of NEs based on natural oils, particularly for the transdermal treatment of various disorders. These oils exhibit multifaceted roles, as they have shown sufficient drug solubilization and permeation enhancement. Moreover, certain essential oils have demonstrated a synergistic effect with certain drugs, whereas others have revealed a remarkable therapeutic outcome when acting alone within the NE. Besides, efforts have been exerted to optimize the performance of these systems by transforming them into nanoemulgels (NEGs) via incorporating them into gelling agents. NEGs provided an easier skin application, a prolonged retention time, and eventually a better transdermal permeability, and most importantly, a more stable system. Based on the increased interest in the field of phytopharmaceuticals and its potential pharmacological activities, researchers are driven to design suitable systems for the transdermal delivery of these agents. This review article highlights the importance of transdermal NEs and NEGs based on natural oils, being cost-effective and easy to manufacture, with an emphasis on their composition, challenges, and future perspectives.
Objective: To rationally design and optimize a eucalyptus oil nanoemulsion through a Quality by Design (QbD) framework while establishing an integrated dual-stability strategy that simultaneously interrogates physicochemical robustness and chemical integrity of eucalyptol under accelerated stress conditions. Methods: Formulation optimization was performed using a full factorial experimental design (2⁴) to investigate the effects of surfactant proportion, cosurfactant proportion, surfactant type, and cosurfactant type on critical quality attributes (CQAs), including percent transmittance and viscosity. Statistical analysis was conducted using analysis of variance (ANOVA), followed by desirability function optimization. Physicochemical stability was evaluated through droplet size, polydispersity index (PDI), pH, viscosity, and visual observation, while chemical stability of eucalyptol was monitored using GC–MS during accelerated storage at 40±2 °C/75±5% RH for three months. Results: The optimized nanoemulsion achieved high optical clarity (92.41%), low viscosity (27.59 cPs), and a desirability value of 0.972, with a statistically significant predictive model for transmittance (R² = 0.9987). The formulation maintained nanoscale droplet size (≈22–25 nm), low PDI (<0.30), stable pH, and absence of phase separation throughout storage. However, GC–MS analysis revealed a time-dependent decline in eucalyptol content despite preserved physicochemical stability, indicating a dissociation between droplet integrity and molecular retention. Conclusion: The proposed integrated dual-stability framework advances current nanoemulsion development paradigms by demonstrating that physicochemical stability alone is insufficient for volatile therapeutic agents. Early incorporation of chemical stability evaluation is essential to achieve formulation reliability and translational relevance.
Objective: The present study investigates the improvement of the solubility of insoluble rifaximin through co-crystallization. Rifaximin is an inhibitor of Ribonucleic acid (RNA) synthesis in susceptible bacteria by binding to the beta-subunit of bacterial Deoxyribonucleic acid (DNA)-dependent RNA polymerase enzyme. Rifaximin belongs to the Biopharmaceutical Classification System (BCS) Class IV, with reduced solubility being the primary concern associated with its use. Methods: Co-crystallization is one method of crystal engineering used to change the physicochemical characteristics of medications that are not very soluble. A co-crystal is a multi-component crystal with non-covalent interactions among the Active Pharmaceutical Ingredients and their co-formers. Auto Dock software was used for the virtual screening of 20distinct co-formers for rifaximin utilizing the molecular docking method. The parameters detected were interaction type and energy (Ei). After analyzing the data of the virtual study, an oxalic acid co-former was selected, and rifaximin co-crystals were fabricated by a solvent evaporation method. Differential Scanning Calorimetry (DSC), Powder X-ray Diffraction (PXRD), Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), In-vitro dissolution, Stability Studies, and Solubility studies were used to characterize co-crystals. The co-crystalized drug was compressed into a tablet dosage form and compared with the in-house formulation of the rifaximin tablet. Results: Molecular docking analysis revealed that oxalic acid exhibited the most favorable interaction with rifaximin, forming four hydrogen bonds with a binding energy of −2.3 kcal/mol, suggesting potential for cocrystal formation. FTIR spectra of the cocrystal showed shifts in the O–H stretch from 3427 cm⁻¹ to 3396 cm⁻¹ and in the C=O stretch from 1720 cm⁻¹ to 1706 cm⁻¹, indicating hydrogen bonding between rifaximin and oxalic acid. DSC thermogram of the cocrystal displayed a single, sharp endothermic peak at 208.52 °C, distinct from pure rifaximin (190.11 °C) and oxalic acid (189.45 °C), confirming the formation of a new crystalline phase. PXRD patterns showed new peaks at 2θ = 12.96°, 16.55°, and 24.42° for the cocrystal, which were absent in the pure drug and co-former, indicating the generation of a novel crystal structure. SEM images revealed significant morphological changes: pure rifaximin appeared as irregular coarse particles, while the cocrystal formed smooth, plate-like crystals with uniform surfaces. Saturation solubility of the cocrystal in 0.375% SLS phosphate buffer (pH 6.8) increased to 2.782 ± 0.21 mg/mL, compared to 0.3892 ± 0.09 mg/mL for pure rifaximin (p < 0.01), representing a 7.1-fold enhancement. The cocrystal-based immediate-release tablet showed 90.25 ± 1.76% drug release at 45 minutes, significantly higher than the pure drug tablet (64.37 ± 2.01%) and the marketed Rexigut tablet (73.15 ± 2.32%). Tablet content uniformity was 98.42 ± 1.6%, disintegration time was 4.8 ± 0.5 minutes, and friability was below 0.5%, meeting pharmacopeial standards. Stability testing under accelerated conditions (40 °C/75% RH) for 3 months showed no significant changes in PXRD patterns or dissolution behavior (post-stability drug release: 89.76 ± 2.01%), indicating physical and chemical stability. Conclusion: Compared to pure rifaximin, these rifaximin co-crystals have significantly improved solubility and in-vitro dissolution. It potentially leads to improved therapeutic outcomes.
Objective: Ibuprofen is hindered in therapeutic application by its poor aqueous solubility. Among various strategies, solid dispersion (SD) emerges as a promising approach. Methods: SD of ibuprofen were formulated using hydroxypropyl cellulose, poloxamer 407, poloxamer 188, PEG 4000, and PEG 6000 with solvent evaporation and fusion method. The water solubility of SDs was compared with non-formulated ibuprofen to identify the most appropriate formulation, which was finally assessed for its saturated solubility, dissolution rate, and physiochemical properties. Results: The results showed that Poloxamer 407 is the most potential carrier for enhancing ibuprofen solubility profile. At 600 mg dose, the saturation solubility of finalized SD showed 85 times higher than raw ibuprofen. At 400 mg dose, the SD achieved over 90% dissolution within 30 min, which was at least 20% higher than both raw ibuprofen and PM. Infrared spectroscopy indicated no incompatibility within the SD after 3 mo of storage at stressed conditions (40 °C, 75% RH). X-Ray diffraction and scanning electron microscope revealed a partial conversion of ibuprofen from crystal state into amorphous state, which was reconfirmed through differential scanning calorimetry and thermogravimetric analysis results. Conclusion: These results highlighted the potential of the SD technique in enhancing the solubility of poorly soluble drugs, which also can be widely applied in pharmaceutical field.
It is now commonly acknowledged that the human gut microbiome, which is made up of a dynamic and complex population of trillions of microbes, plays a significant role in controlling human health and illness. A growing body of research demonstrates its role in the development and spread of many types of cancer, as well as its impact on how well cancer treatments work. Through persistent inflammation, DNA damage, immune evasion, metabolic changes, and epigenetic modifications, dysbiosis—an imbalance in the microbial ecosystem—contributes to carcinogenesis. Additionally, the gut flora influences the toxicity and effectiveness of radiation, immunotherapy, and chemotherapy. This study offers a thorough assessment of recent discoveries relating the gut microbiota to the development of cancer and treatment results. Cancer-specific microbial fingerprints across key tumor types are described, coupled with the mechanistic mechanisms of microbiota-driven carcinogenesis. Probiotics, prebiotics, postbiotics, fecal microbiota transplantation (FMT), and microbiome-targeted therapies are among the new therapeutic approaches that are also rigorously examined. This study highlights prospects for incorporating microbiome science into precision oncology by resolving current obstacles and knowledge gaps, opening the door to individualised cancer prevention and therapy.
Objective: The purpose of this investigation was to create a tablet containing nifedipine for extended-release by laser drilling technique using a resolution IV 24-1 fractional factorial design. Methods: The extended-release tablet formulation bearing nifedipine was developed by the wet granulation method. The A resolution IV 24-1fractional factorial design was employed to optimize the nifedipine extended-release tablets. The ratio of sodium chloride (NaCl) to polyox water soluble resin (WSR) NEO, the ratio of NaCl to polyox WSR Coagulant LEO in the push layer, the ratio of polymer and plasticizer in extended release (ER) coat, and % weight gain in the extended-release coat were taken as independent variables, and the percentage of drug dissolved was taken as the dependent variable. The resolution IV 24-1 fractional factorial design was utilized to optimize the formulation, which was subsequently assessed for its performance such as mean weight, thickness, hardness, and friability. Finally, optimized laser-drilledtablets were compared with the undrilled nifedipine extended-release tablets for percent drug release. Results: The mean weight of the optimized formulation was found to be 718 ± 2.5 mg, the mean thickness was measured to be 7.51± 0.2mm, the hardness of the tablet was found to be 130 ± 5 N, tablet friability was measured as 0.9 ± 0.1% and finally the drug release study of tablets having précised orifice shows controlled drug release over a period of time. Conclusion: The developed nifedipine extended-release formulation demonstrated controlled drug release following laser drilling. The laser-drilled tablets exhibited a sustained release profile over the study period. The results indicate that laser drilling is a feasible approach for modulating drug release from extended-release tablets.
