Journal of Applied Pharmaceutical Research

Advances in herbal and synthetic transferosomes: routes, formulation challenges and comparative performance

2026-04-17T09:11:30+00:00

Background: Transferosomes are ultra-deformable vesicular carriers widely investigated for enhancing drug delivery across biological barriers. Both herbal and synthetic transferosomes have gained attention for improving permeability, bioavailability, and therapeutic efficacy. However, a comparative understanding of their formulation strategies, therapeutic performance, and associated challenges remains limited. Methodology: A systematic literature review was conducted to compare herbal and synthetic transferosomes. A total of 100 research and review articles were analyzed, including 50 studies each on herbal and synthetic formulations. Data were categorized based on formulation benefits, challenges, routes of administration, and dosage forms, and analyzed to determine the frequency of these parameters. Results and Discussion: Synthetic transferosomes exhibited higher permeability (30%), stability (18%), solubility (10%), and vesicle deformability (13%) due to their defined composition and controlled formulation. However, scalability 27%, vesicle size control, and encapsulation efficiency remained major challenges. Herbal transferosomes demonstrated improved bioavailability (20%) and drug delivery efficiency (18%), likely due to the synergistic effects of phytoconstituents. Nevertheless, they showed greater extract variability (28%) and formulation instability (18%). Transdermal delivery was the predominant route, accounting for 80% of herbal and 65% of synthetic formulations, with gels being the most common dosage form. Conclusion: Synthetic transferosomes provide better formulation control and reproducibility, whereas herbal systems offer enhanced therapeutic potential. Optimization of formulation parameters and stability is essential to improve the translational applicability of both systems.

Solid self-microemulsifying drug delivery systems in modern pharmaceutics: design, characterization, and clinical applications

2026-05-26T08:29:39+00:00

Background: Approximately 40% of marketed medicines and 70% of pipeline products exhibit poor aqueous solubility, leading to inconsistent oral bioavailability and impaired efficacy. S-SMEDDS represent a revolutionary approach for converting liquids into stable solid dosage forms. Methodology: Methods employed to prepare S-SMEDDs include adsorption onto carriers, spray drying, hot-melt extrusion, and freeze-drying. Characterization includes assessing self-emulsifying behavior, dynamic light scattering, powder diffraction, and thermal analysis. Results and Discussion: Depending on the drug's characteristics, the formulation composition, and the study conditions, S-SMEDDS can increase bioavailability by two to ten times. However, for some extremely lipophilic BCS Class II and IV pharmaceuticals, significantly greater benefits (up to ~50-fold) have been documented. Several investigations have demonstrated that S-SMEDDS exhibit better physical and chemical stability than liquid systems under ICH Q1A(R2) accelerated storage conditions due to reduced lipid mobility and a lower risk of phase separation. Applications extend to the treatment of cardiovascular, oncological, and endocrine disorders with improved pharmacodynamic efficacy. The multiple absorption mechanisms in S-SMEDDS include improved solubilization, reduced precipitation, lymphotropic delivery, and inhibition of efflux pumps. They demonstrate higher chemical and physical stability, precise dosing, and better patient adherence when compared to traditional liquid counterparts. Conclusion: S-SMEDDS constitute an established pharmaceutical platform that overcomes the drawbacks associated with liquid lipid drug delivery systems. Their high effectiveness, manufacturability, and compatibility with novel technologies such as three-dimensional printing and artificial intelligence position them to be the foundation for precision oral drug delivery.

A review of silver nanoparticle synthesis methods and their functional applications

2025-04-24T10:00:57+00:00

Background: The growing interest in the biosynthesis of nanoparticles, particularly silver nanoparticles (AgNPs), has gained massive attention due to their wide range of applications in electronics, biosensors, optics, catalysis, food, and environmental fields. Medical applications of AgNPs are mainly attributed to their substantial antimicrobial property and their relatively low toxicity under appropriate conditions. Plant extracts are more convenient, offering an eco-friendly, cost-effective approach that uses phytochemicals as natural reducing and stabilizing agents. However, a major gap is the lack of standardized synthesis techniques, leading to inconsistent nanoparticle properties and biological efficacy. Methodology: This review aims to provide a detailed study of the diverse synthesis routes of AgNPs and their applications. The study focuses on the impact of plant extract composition on other synthesis conditions. Characterization of nanoparticles is also discussed. Results and Discussion: Studies have shown that plant-derived AgNPs demonstrate better antimicrobial activity against various microorganisms, including bacteria and fungi. AgNPs synthesized from Ipomoea asarifolia exhibited strong antibacterial activity (IC₅₀ of 1 μg/mL) against bacterial pathogens. AgNPs produced using Cocos nucifera leaf extract showed significant antibacterial activity, with the highest activity against Citrobacter freundii (20 mm) and Pseudomonas aeruginosa (19 mm). AgNPs synthesized from Ricinus communis extracts remained stable at temperatures up to 100 °C and within a pH range of 5–6 for several months. Conclusion: The present review details the factors affecting the synthesis of AgNPs. Furthermore, it provides an overview of scalability challenges and the underlying molecular mechanisms in current research.

A review on skin aging: mechanisms and therapeutic strategies

2026-05-03T17:41:14+00:00

Background: Skin aging is a complex process driven by multiple factors. In addition to hereditary factors and cellular aging, exposure to sunlight, air pollution, and lifestyle factors are extrinsic factors that stress the skin. Skin aging involves multiple biological processes influenced by both internal factors (age, skin type, cellular aging) and external factors such as ultraviolet radiation, air pollution, and lifestyle. These cause various changes in appearance, function, and structure. Methodology: An extensive search of the published scientific literature on the mechanisms of skin aging and anti-aging treatments was conducted. Articles related to oxidative stress, inflammation, ECM degradation, melanogenesis, and signaling pathways, including MAPK, NF-κB, Nrf2, TGF-/Smad, and mTOR, were critically reviewed. Results and Discussion: The evidence indicates that skin aging is associated with the production of reactive oxygen species (ROS), DNA lesions, persistent inflammation, collagen lysis, and defective cellular regenerative processes. Current novel interventions, including antioxidants, senolytics, stem cell therapy, telomere-shifting, epigenetic-modifying approaches, and Mitochondrial therapy directed toward mitophagy, have shown noteworthy effects in reducing the progression of skin aging. Also, herbal topical preparations containing bioactive phytoconstituents have proven to be a safe and effective modality. Conclusion: Skin aging is a result of an intricate network of cross-interrelated intrinsic and extrinsic factors involving various molecular pathways. Novel, more effective, and safer therapeutic approaches and preparations of bioactive herbal formulations appear promising for treating skin aging.

Quality by design based optimization and physicochemical characterization of flucytosine nanoemulsion

2026-04-17T09:38:04+00:00

Background: The rise of pathogenic fungi capable of infecting people is a major public health problem. Flucytosine is an effective antifungal agent, but its clinical use is constrained by rapid clearance and dose-related adverse effects. Nanoemulsion-based systems offer a promising strategy for drug delivery and therapeutic performance. The objective of this work was to develop and optimize a flucytosine-loaded nanoemulsion using a Quality by Design (QbD) approach based on the Box-Behnken design, and to evaluate its physicochemical characteristics. Methodology: A Box-Behnken design (BBD) was used to optimize formulation factors, including lipid concentration, Smix (surfactant-to-cosurfactant) ratio, and homogenization time, using high-speed homogenization. The impacts on particle size, polydispersity index, and entrapment efficiency (EE) were investigated. UV-visible spectroscopy, Fourier-transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD) were used to assess the compatibility and stability of the improved formulation (F11) with the chosen excipients. Results and Discussion: The optimized formulation (F11) had a particle size of 318.18 nm and a PDI of 0.136, a zeta potential of -22.2 mV, and high entrapment efficiency (96.36%), indicating good stability and uniformity. Preformulation and compatibility studies confirmed the absence of drug-excipient interactions. Statistical analysis demonstrated that formulation variables significantly influenced critical quality attributes. Conclusion: The study demonstrates that QbD-driven optimization can successfully develop a stable and efficient flucytosine nanoemulsion with enhanced drug-loading capacity and potential to improve antifungal therapy. However, further studies, including in vitro drug release, in vivo evaluation, long-term stability, and clinical validation, are required to confirm its performance in drug delivery applications.

Green solvent-assisted development of UV-spectrophotometric and RP-HPLC methods for telmisartan and efonidipine HCl ethanolate

2026-04-17T10:51:49+00:00

Background: Hypertension is a prevalent cardiovascular disorder requiring effective therapeutic strategies. Telmisartan, an angiotensin II receptor antagonist, and Efonidipine HCl Ethanolate, a calcium channel blocker, are often co‑administered for synergistic blood pressure control. To ensure the quality and efficacy of pharmaceutical formulations, it is essential to develop simple, precise, and eco-friendly analytical methods for their simultaneous estimation and validation in accordance with ICH Q2(R1) guidelines. Methodology: Two UV spectroscopic methods and one RP‑HPLC method were developed and validated. Method A employed the simultaneous equation approach using absorbance values at 297 nm and 251 nm, corresponding to the λmax of Telmisartan and Efonidipine, respectively. Method B utilized the area under the curve (AUC) method for simultaneous quantification. The RP‑HPLC method was performed on an Agilent C18 column (250 × 4.6 mm, 5 μm) with isocratic elution using ethanol and 0.1% orthophosphoric acid in water (85:15 v/v) at a flow rate of 0.9 mL/min, and detection was at 253 nm. Results and Discussion: All three methods demonstrated excellent linearity, precision, and accuracy within validated ranges. Recovery studies confirmed reliability, with values within acceptable limits. The UV method (Greenness score 92) is slightly greener than HPLC (Greenness score 88), with both demonstrating excellent eco-friendly performance. The UV methods offer rapid and economical screening, while RP‑HPLC ensures high sensitivity and specificity. The use of ethanol as a green solvent supports eco‑friendly pharmaceutical analysis. Conclusion: Validated UV and RP‑HPLC methods were successfully developed for simultaneous estimation of Telmisartan and Efonidipine HCl Ethanolate. These approaches are robust, precise, economical, and environmentally sustainable for routine quality control in pharmaceutical dosage.

Formulation, box-behnken optimization, and evaluation of lurasidone HCl-loaded ethosomal gel for transdermal delivery

2026-02-14T07:38:08+00:00

Background: Lurasidone HCl is an antidepressant drug, which is available in solid dosage form in the market. The drug lurasidone HCl in the tablet form shows poor oral bioavailability, which is only 9- 19%. Therefore, an alternative dosage form, such as ethosomes, is preferred. Methodology: The thin film hydration technique was used to formulate ethosomes. A Box-Behnken design was used to optimize the formulation, with statistical and graphical analyses of the response surface plots. Ethanol (X1), phosphatidylcholine (X2), and penetration enhancer (X3) were selected as the independent variables, and the dependent variables were vesicle size (Y1), zeta potential (Y2), and entrapment efficiency (Y3). An optimized formulation was selected after characterization of ethosomes. The optimized ethosomal formulation was incorporated into a gel base. Various ratios of Pluronic F 127 and carbopol 934 were used to prepare gel formulations, which were then evaluated. Results and Discussion: Microscopic examination of formulated ethosomes shows results within the standards. After 24 hours of study, the percentage of drug permeated was 94.7 ± 0.153. A Box-Behnken design was used to prepare and optimize ethosomes. Optimized ethosomes exhibited a vesicle size of 276.8 nm, a zeta potential of -55.7 mV, and an entrapment efficiency of 90%. Carbopol gel base was used to prepare the gel and evaluated. Conclusion: The optimized ethosomal formulation was selected for preparing an ethosomal gel loaded with lurasidone HCl. The prepared gel formulations were evaluated, and all showed satisfactory results, indicating that ethosomes are the best alternative route for administering lurasidone HCl.

Design, optimization and evaluation of an ion-triggered in situ nasal gel of selegiline for antidepressant therapy

2026-04-15T04:18:09+00:00

Background: Oral delivery of selegiline is limited by extensive first-pass metabolism, low and variable bioavailability, and restricted brain access due to the blood–brain barrier. Intranasal drug delivery offers a non-invasive strategy for direct nose-to-brain transport. The present study aimed to design, optimize, and evaluate an ion-triggered in situ nasal gel of selegiline using sodium alginate and HPMC to potentiate brain delivery and antidepressant efficacy. Methodology: Preliminary screening was performed using the Plackett–Burman design to identify critical formulation variables. Further optimization was carried out using the Box–Behnken design with sodium alginate (0.5–2% w/v), HPMC (0.5–1% w/v), and CaCl₂ (10–50 mM) as independent variables. The optimized formulation was evaluated for physicochemical properties, rheology, gelation time, gel strength, mucoadhesive strength, in vitro and ex vivo drug release, histopathology, in vivo antidepressant activity, and stability. Results and Discussion: The optimized formulation (1.25% sodium alginate, 0.75% HPMC, 30 mM CaCl₂) exhibited suitable sol viscosity (~150 mPa·s), rapid gelation (~34 s), adequate gel strength (~350 g), and good mucoadhesive strength (~3140 dyne/cm²). Sustained drug release (~98% in 8 h in vitro; ~94% in 6 h ex vivo) was achieved. The formulation was non-irritant to nasal mucosa, showed enhanced antidepressant activity in vivo, and remained stable for 3 months under stability studies. Conclusion: The optimized sodium alginate–HPMC ion-triggered in situ nasal gel of selegiline offers a safe, stable, and effective nose-to-brain delivery system with sustained release and improved antidepressant activity, making it a promising alternative to oral therapy.

Improving the biopharmaceutical performance of azole antifungals: a comparative study of solid dispersion and co-crystallization of ketoconazole and itraconazole

2026-02-26T07:09:19+00:00

Background: Oral bioavailability of BCS class II azole antifungals, ketoconazole and itraconazole, is hampered by low aqueous solubility. Improving solubility and dissolution is necessary for greater therapeutic efficacy. This research compared two approaches: solid dispersion and pharmaceutical co-crystallization to improve their biopharmaceutical properties. Methodology: Solid dispersions were prepared using the organic solvent evaporation technique with PEG-10000 for ketoconazole and HPMCE50 for itraconazole. Co-crystals with benzoic and tartaric acids were studied by FT-IR, DSC, and PXRD. Optimized formulations were compressed into tablets and analyzed for pharmacopoeial parameters, dissolution, release kinetics, and ICH stability. Results and Discussion: Saturation solubility investigations revealed that, compared to amorphization, solid dispersions exhibited more efficient enhancement due to the combined effect of amorphous enrichment and polymer solubilization. Tartaric acid co-crystals could increase solubility by crystal lattice modification. cc-Tabs showed burst release profiles, while SDs gave controlled drug release. The release of drug was in accordance with the first-order and Korsmeyer–Peppas models with anomalous transport, and was sustained for six months. The low aqueous solubility of azole antifungals restricts their oral bioavailability. The solubility and dissolution of ketoconazole and itraconazole were enhanced by solid dispersion and co-crystallization. Solid dispersions provided superior amorphous stability and extended-release, while co-crystals led to faster initial dissolution and better early drug availability. Conclusion: Both approaches were successful in improving solubility, dissolution, and stability. Both SDs modulated drug release kinetics; sustained-release profiles were obtained from the solid dispersions, and fast dissolution was favored by co-crystallization, thus providing both as viable approaches for oral delivery of poorly soluble azole antifungals.

Bilayer mucoadhesive intrauterine delivery platform for sustained platelet-derived extracellular vesicle release to promote endometrial regeneration and improve implantation outcomes

2026-02-23T17:56:36+00:00

Background: Endometrial dysfunction remains a major cause of implantation failure and infertility. Extracellular vesicles (EVs) derived from platelet-rich plasma have shown regenerative potential; however, their clinical application is limited by rapid clearance and poor retention within the uterine cavity. Methodology: A bilayer mucoadhesive intrauterine delivery platform was developed for sustained release of platelet-derived extracellular vesicles. The bilayer system consisted of a mucoadhesive EV-loaded layer and a protective anti-adhesion layer. Physicochemical characterization, EV release kinetics, and mucoadhesion properties were evaluated. In vitro wound healing, cell proliferation, and gene expression studies were performed. In vivo efficacy was assessed through histological evaluation of endometrial thickness and implantation outcomes. Results and Discussion: The bilayer platform demonstrated sustained extracellular vesicle release for up to 120 h with minimal initial burst release. Enhanced cell migration and proliferation, along with upregulation of endometrial receptivity markers including LIF, HOXA10, Integrin αV/β3, and IGFBP1, were observed. In vivo studies revealed significant improvement in endometrial thickness and implantation sites in the EV-Pad group compared to controls. The sustained release of EVs improved endometrial regeneration and enhanced implantation potential. The bilayer design demonstrated improved local retention characteristics and enhanced regenerative responses compared with free EV administration under experimental conditions. Conclusion: The developed bilayer mucoadhesive intrauterine delivery system provides a promising strategy for sustained EV delivery and improved endometrial regeneration, supporting its potential as a preclinical platform for sustained intrauterine regenerative delivery.

Protective effects of Pithecellobium dulce seed extract on sodium fluoride-induced neurotoxicity in rats

2026-01-03T06:26:52+00:00

Background: According to epidemiological research, fluoride is a developmental neurotoxicant that lowers children's IQ scores. Fluoride induces oxidative stress in the brain, which can cause histological damage. This study aims to test the antioxidant potential of the methanolic extract of Pithecellobium dulce seeds. Methodology: By using different in vivo assays such as inhibition of DPPH activity in plasma, Glutathione Peroxidase (GSH-Px) activity in the brain, and histology of the cerebral cortex on days 1, 10, 20, and 30 with both Hematoxylin &Eosin and Cresyl violet stains. Results and Discussion: The methanolic extract of P dulce seeds significantly enhances GPx activity in a dose-dependent manner, effectively countering oxidative stress and providing neuroprotective benefits against fluoride-induced neurodegeneration. Results also showed the strong antioxidative potential of PDME, particularly in mitigating NaF-induced oxidative stress, as evidenced by sustained high DPPH radical-scavenging activity in the treated groups over time. An H&E histology study highlights the neuroprotective effects of PDME against NaF-induced neurodegeneration, demonstrating that PDME treatment significantly reduces neuronal loss and preserves cellular integrity, particularly at higher doses. Cresyl violet stain demonstrates that PDME has a neuroprotective effect against NaF-induced neurotoxicity, as evidenced by the preservation of neuronal morphology and Nissl substance. The study demonstrates that the methanolic extract of Pithecellobium dulce seeds exhibits significant antioxidant activity, effectively counteracting fluoride-induced neurotoxicity and preserving neuronal integrity by enhancing glutathione peroxidase activity and improving histological outcomes. Conclusion: These findings suggest that P. dulce may serve as a potential neuroprotective agent against fluoride-related cognitive impairments.

Design, development and optimization of tedizolid phosphate carbopol based emulgel for skin drug delivery

2026-01-24T00:48:17+00:00

Background: Tedizolid phosphate (TZP) is effective against Gram-positive pathogens. It is used most widely in skin infections. Currently, there is no development of emulgels with this novel antibiotic molecule. Hence, the current research focused on developing emulgels for effective topical antimicrobial action to overcome disadvantages associated with oral drug delivery. Methodology: The drug spectroscopic method was developed using a UV-visible spectrophotometer. The o/w emulsions were prepared and incorporated into a gel base to form an emulgel. The prepared emulgels were subjected to physicochemical, IR spectral, antimicrobial, and biophysical analysis. Results and Discussion: Physical examination revealed clear emulgel texture for all test formulations, with maximum spreadability and rheology for carbopol 934 compared to HPMCK 15 and sodium CMC bases. The optimized carbopol 934-based EF7 formulation showed 86% in vitro drug release and 73% ex vivo drug release in 12 hours, respectively. The FTIR studies clearly indicate no incompatibility among the drug and excipients. All physicochemical parameters confirmed controlled release, and FTIR studies confirmed no incompatibility. The optimized emulgel showed good bacterial growth inhibition, and pathological studies confirmed the absence of alteration of porcine ear skin structure. Conclusion: The results indicate that the optimized formulation is suitable for the treatment of acute skin infection.

Novel chemometric-driven greenness assessed spectroscopical method development and forced degradation study of sitagliptin phosphate in its bulk drug and ophthalmic formulation

2026-04-23T17:58:55+00:00

Background: Sitagliptin phosphate (SIT), an antidiabetic drug, requires reliable analytical methods for routine quality control and stability assessment. UV-visible spectrophotometry offers a simple and economical approach; however, method robustness and stability-indicating capability must be ensured using systematic development strategies such as Quality by Design (QbD). The objective of this work is to develop and validate a rapid, simple, economical, accurate, and precise UV-visible spectrophotometric method with a stability-indicating capability for the analysis of SIT in bulk drug and ophthalmic formulation. Methodology: Method development was performed using a QbD approach in a quality control laboratory with a UV-visible spectrophotometer and 1 cm quartz cells. Various solvents (phosphate buffer, ethanol, acetonitrile, methanol, and water) were evaluated, with water selected due to superior solubility and spectral characteristics. SIT showed maximum absorbance at 265-267 nm. Forced degradation studies (acidic, basic, oxidative, thermal, and photolytic) were conducted. Validation was performed as per ICH Q2 (R1) guidelines. Results and Discussion: The developed method exhibited excellent linearity (R² ≥ 0.998), accuracy (99-101% recovery), and precision (%RSD ≤ 2%). Recovery ranged from 98.68% to 99.46%. The method was robust and successfully indicated stability under stress conditions. The application of QbD ensured systematic optimization and robustness. Water proved to be an ideal solvent, enhancing method simplicity and cost-effectiveness. The method effectively distinguished SIT from degradation products, confirming its stability-indicating nature. Conclusion: A validated, reliable, and economical UV-visible spectrophotometric method was successfully developed for SIT analysis, suitable for routine quality control and stability studies in bulk drug and ophthalmic formulations.

Formulation and evaluation of factorial design based sulfasalazine-loaded ethosomal gel for rheumatoid arthritis

2026-02-19T08:50:28+00:00

Background: Oral administration of sulfasalazine for rheumatoid arthritis is associated with limitations that reduce therapeutic effectiveness. Transdermal delivery using ethosomal vesicles offers a promising strategy to enhance skin penetration and provide localized therapeutic effects. Methodology: Sulfasalazine-loaded ethosomes were formulated using the cold method and optimized using a 3² full factorial design across nine experimental trials. The formulations were characterized for vesicle size, polydispersity index (PDI), zeta potential, entrapment efficiency, and morphology using atomic force microscopy (AFM). The optimized ethosomal formulation was incorporated into a 1% Carbopol 934 gel to prepare the ethosomal gel (EGL). Ex vivo permeation studies were performed using rat skin to compare EGL with a conventional gel (CGL), and flux and permeability coefficients were calculated. Anti-inflammatory activity was assessed in Sprague–Dawley rats. Results and Discussion: Particle sizes ranged from 98.3 ± 2.37 nm to 187.7 ± 3.12 nm, with a negative zeta potential ranging between –24.2 ± 2.56 mV and –32.6 ± 1.35 mV. The entrapment efficiency ranged from 85.33 ± 3.84% to 94.62 ± 1.34%. Vesicles displayed smooth and spherical surfaces. In vitro drug release studies of the ethosomal gel formulations lasted 12 hours, revealing controlled release of sulfasalazine and enhanced ex vivo permeation in the optimized formulation. In vivo studies showed that EGL produced a greater reduction in inflammation compared to CGL. Conclusion: The developed ethosomal gel demonstrated enhanced skin permeation and anti-inflammatory efficacy, making it a promising transdermal delivery system for sulfasalazine in the management of rheumatoid arthritis.

Anxiolytic activity of methanolic leaf extracts of Amaranthus cruentus Linn. and Rumex acetosa Linn. in mice

2026-01-20T08:08:09+00:00

Background: The current study aims to define the anti-anxiety properties of the leaves of Amaranthus cruentus Linn. and Rumex acetosa Linn. Methodology: Soxhlet extraction was used to extract the leaves of Rumex acetosa Linn and Amaranthus cruentus Linn. FTIR and GC-MS were used to investigate the fraction. The elevated plus maze test (EMPT) was used to assess the antianxiety property of methanolic extracts at 200 mg/kg and 400 mg/kg in Swiss albino mice. Results and discussion: Alkaloids, steroids, glycosides, amino acid flavonoids, carbohydrates, and phenolic tannins are found in both extracts. The percentage yields of petroleum ether, chloroform, and methanol extracts were 2.4%, 3.6%, and 10% for Amaranthus cruentus, and 2.1%, 3.2%, and 8% for Rumex acetosa, respectively. Amaranthus cruentus extracts were associated with significant increases (P < 0.05) in the amount of time and the number of entries in open arms. Open arm entries (p < 0.01) and time spent in the open arm (p < 0.01) were both increased by 200 mg/kg of Rumex acetosa Linn extract, while 400 mg/kg increased both of these variables (p < 0.001). Nevertheless, activity rises in tandem with the dosage of Rumex acetosa Linn extract. In EMPT, diazepam (2 mg/kg) significantly increased open arm entries (22.67) and time spent in open arms (3.273 min), while decreasing closed arm entries (6.33) and time spent in closed arms (1.582 min) compared to the control group, confirming its potent anxiolytic activity. Conclusion: The methanolic extracts of both plants exhibit significant anxiolytic properties.

Synthesis, spectral characterization, and in vitro anticancer evaluation of novel Flavanone-arylhydrazone derivatives

2026-04-03T03:43:33+00:00

Background: Flavanones are naturally occurring scaffolds with diverse pharmacological activities, including anticancer potential. Structural modification through hydrazone incorporation may enhance their biological properties and support the development of new therapeutic leads for breast cancer. Methodology: A series of nine flavanone-arylhydrazone derivatives was synthesized via condensation of substituted flavanones with phenylhydrazines under reflux conditions. The structures were confirmed using IR, ¹H NMR, and high-resolution mass spectrometry (HRMS). The compounds were evaluated for in vitro cytotoxicity against MCF-7 and MDA-MB-231 breast cancer cell lines using the MTT assay, with tamoxifen as the reference drug. Results and Discussion: All synthesized compounds exhibited dose-dependent cytotoxicity. Derivatives bearing electron-withdrawing substituents, such as nitro and halogen groups, showed relatively enhanced activity. Compounds 3 and 1 demonstrated the lowest IC₅₀ values (33–44 µM), indicating comparatively higher potency within the series. However, only modest differences in activity were observed among derivatives, suggesting that electronic effects alone do not fully govern cytotoxicity. Conclusion: Flavanone-arylhydrazone hybrids represent a promising scaffold for anticancer drug development. While electron-withdrawing substituents contribute to activity, the overall structure–activity relationship appears to be influenced by multiple physicochemical factors. Further mechanistic and in vivo studies are required to establish their therapeutic potential.

Enhanced selectivity in alpelisib quantification in human plasma: a validated LC-MS/MS method with deuterated internal standard

2026-05-14T08:31:27+00:00

Background: To enhance efficacy and manage dose-limiting toxicities such as hyperglycemia, therapeutic drug monitoring of alpelisib (ALB), a phosphatidylinositol 3-kinase alpha (PI3Kα) inhibitor used in advanced breast cancer, is essential. This study aimed to develop and validate a selective, sensitive, and high-throughput liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification of ALB in human plasma to support pharmacokinetic studies and therapeutic drug monitoring. Methodology: Alpelisib-D3 was used as a deuterated internal standard (IS). Analytes were extracted from 50 µL of plasma by liquid-liquid extraction using n-hexane and methyl tert-butyl ether (20:80, v/v). Chromatographic separation was performed on an X-Terra RP8 column using an isocratic mobile phase of 5 mM ammonium acetate buffer (pH 5.00) and acetonitrile (10:90, v/v) at 0.4 mL/min. Detection was carried out in positive electrospray ionization mode using multiple reaction monitoring of m/z 442.15→141.07 for ALB and m/z 445.36→144.05 for the IS. Validation included linearity, precision, accuracy, recovery, matrix effect, carryover, dilution integrity, and stability. Results and discussion: The method was linear over 50.0–10,000 ng/mL. Intra- and inter-day precision (CV%) was <4.2%, and accuracy ranged from 94.5% to 106.2%. Mean extraction recovery exceeded 90%, with no significant matrix effects. Carryover, stability, and dilution integrity also met acceptance criteria. Conclusion: A reliable, sensitive, and selective LC-MS/MS method was successfully developed and validated. The method is suitable for high-throughput pharmacokinetic studies and therapeutic drug monitoring of ALB in human plasma.

Polyphenol-rich fraction of Thalassia hemprichii: dual enzyme inhibition, antioxidant capacity, and anti-inflammatory activity for diabetes management

2025-11-28T06:39:10+00:00

Background: Diabetes mellitus is a chronic metabolic disorder marked by hyperglycemia and associated complications. Limitations of current therapies have driven interest in marine-derived bioactives, particularly polyphenols, for safer and multi-targeted interventions. Thalassia hemprichii, a tropical seagrass rich in phenolic compounds, remains underexplored for antidiabetic potential. Methodology: A polyphenol-rich fraction (PRF) was extracted from T. hemprichii leaves using sequential solvent extraction. FTIR spectroscopy was employed to identify functional groups. Total phenolic and flavonoid contents were quantified using spectrophotometric methods. In vitro antidiabetic activity was assessed by α-amylase inhibition (DNSA method) and α-glucosidase inhibition (pNPG assay), with acarbose as the reference, and anti-inflammatory and antioxidant assays were also performed. Results and Discussion: FTIR analysis confirmed the presence of hydroxyl, carbonyl, and aromatic groups, indicating the presence of phenolic compounds. PRF demonstrated dose-dependent inhibition of α-amylase (13.4–55.6%) and α-glucosidase (16.72–58.14%) at concentrations of 25–125 μg/mL, with IC₅₀ values comparable to acarbose. The inhibitory profile showed stronger activity against α-glucosidase and moderate suppression of α-amylase. In addition, PRF exhibited significant antioxidant (49.40–78.23%) and anti-inflammatory (40.78–75.02%) effects in a concentration-dependent manner (50–200 μg/mL). Conclusion: The polyphenol-rich extract of T. hemprichii exhibits notable dual-enzyme inhibition, indicating its potential to manage postprandial hyperglycemia while reducing gastrointestinal side effects. Its cytoprotective properties, including antioxidant and anti-inflammatory activities, further support its role in preventing diabetes-related complications. These findings highlight T. hemprichii as a promising candidate for nutraceutical or phytopharmaceutical development, meriting further in vivo validation and safety evaluation.

Formulation, optimization and characterization of apremilast-loaded nanosponges for potential topical wound management applications

2026-04-10T11:29:07+00:00

Background: Topical drug delivery systems provide site-specific therapy with reduced systemic exposure. Nanosponges have emerged as promising carriers owing to their porous structure, enabling improved drug stability, bioavailability, and sustained release. Apremilast, a phosphodiesterase-4 (PDE4) inhibitor with anti-inflammatory activity, has potential for topical wound management when formulated as a controlled-release delivery system. Methods: Apremilast-loaded nanosponges were prepared by the emulsion solvent diffusion method using Ethyl Cellulose (EC) and Polyvinyl Alcohol (PVA). A 3² factorial design was used to optimize the EC: PVA ratio and sonication time. Formulations were evaluated for particle size, entrapment efficiency, zeta potential, in vitro drug release, and surface morphology. Characterization included UV spectroscopy, FTIR, XRD, DSC, and SEM. Drug release kinetics were analyzed using mathematical models. Results: Preformulation studies confirmed drug purity and compatibility with excipients. The optimized formulation (NS8) exhibited a particle size of 213.85 nm, an entrapment efficiency of 82.75%, a zeta potential of −33.3 mV, and a sustained drug release of 95.85% over 24 h. SEM revealed spherical porous nanosponges, while FTIR, XRD, and DSC confirmed drug integrity and formulation stability. Response surface analysis demonstrated significant effects of formulation variables on performance. Drug release followed the Higuchi model (R² = 0.987), and the Korsmeyer–Peppas exponent (n = 0.58) indicated anomalous non-Fickian diffusion. Conclusion: Apremilast-loaded nanosponges demonstrated sustained drug release, excellent stability, and favorable physicochemical characteristics, indicating their potential as an effective topical delivery system for wound management. Further ex vivo, in vivo, and clinical studies are required to confirm therapeutic efficacy and safety.

Creation and verification of an RP-UHPLC technique for abemaciclib and associated impurities in formulations and APIs using Box-Behnken design

2026-04-04T07:00:05+00:00

Background: Strict impurity profiling is necessary to ensure the safety, effectiveness, and regulatory compliance of Abemaciclib (AbB), a selective CDK4/6 inhibitor frequently used in breast cancer treatment. However, a lack of thorough impurity separation, lengthy run times, and low sensitivity are common problems with current analytical techniques. Methodology: A novel reverse-phase ultra-high-performance liquid chromatography (RP-UHPLC) method was developed using a Quality by Design (QbD) framework. Critical method parameters, including mobile phase pH, flow rate, and column temperature, were optimized using Box-Behnken Design (BBD). Chromatographic separation was achieved on a C18 column using an isocratic mobile phase consisting of acetonitrile (40:60, v/v) and ammonium formate buffer (pH 2.7). The technique was validated in accordance with the ICH Q2(R1) requirements. Results and Discussion: The optimized method demonstrated exceptional linearity over the range of 0.02–150 μg/mL (R² > 0.999) with excellent precision (RSD < 2% for AbB and < 10% for related impurities) and showed acceptable accuracy, with mean recoveries ranging from 92.76% to 102.88% across AbB and its related impurities. The detection and quantification limits for AbB were 0.01 μg/mL and 0.02 μg/mL, respectively. Forced degradation studies that effectively distinguished degradation products in oxidative, acidic, and alkaline settings confirmed the method's stability-indicating nature. The 8-minute run time allowed for quick examination. The integration of BBD-based QbD significantly enhanced method robustness, resolution, and sensitivity compared to conventional chromatographic approaches, allowing simultaneous quantification of AbB and its related impurities. Conclusion: For routine quality control, stability investigations, and regulatory-compliant impurity profiling of Abemaciclib, the developed RP-UHPLC method is quick, sensitive, reliable, and appropriate.

Factors influencing anti-osteoporotic medicine consumption in Uzbekistan: A descriptive analysis

2026-01-24T18:25:55+00:00

Background: Osteoporosis is an increasing public health burden in Uzbekistan, driven by demographic changes and limited access to timely diagnosis and treatment. This study aims to identify key determinants influencing the consumption of anti-osteoporotic medicines (AOMs). Methodology: A multifactor analytical approach was applied using descriptive, grouping, and correlational methods, as well as compound annual growth rate (CAGR) analysis. Because the annual series deviated from normality, associations between variables were assessed using Spearman’s rank correlation coefficient (ρ). As CAGR is a descriptive indicator, the statistical significance of temporal change was additionally evaluated using Spearman’s rank-based trend analysis. Results: Osteoporosis incidence increased by 95% between 2016 and 2024, with pronounced regional variability. The national CAGR was 9%, although the monotonic national time trend did not reach statistical significance (ρ = 0.533, p = 0.139). In RSSPMTO data, the correlation between annual population size and the combined number of osteoporosis/osteopenia cases was moderate when 2022 was included (ρ = 0.60, exact p = 0.350) and higher after exclusion of the 2022 peak (ρ = 0.80, exact p = 0.333). Still, neither association reached statistical significance, likely due to the small number of observations. Discussion: The findings indicate that medical, demographic, and technological factors, particularly limited diagnostic capacity and uneven regional detection, may influence AOMs consumption. Conclusion: Improving access to AOMs in Uzbekistan requires expanding densitometry services, implementing screening programs, and strengthening pharmaceutical policy through reference pricing, domestic production incentives, and price regulation.

Design, optimization of bio flexible films of sumatriptan succinate and naproxen sodium via oro trans soft palatal delivery

2026-05-07T05:40:44+00:00

Background: Bio-flexible films are polymeric drug delivery systems designed to enhance systemic drug absorption through the oral mucosa. This study aimed to develop and optimize bio-flexible, mucoadhesive films containing Sumatriptan Succinate and Naproxen Sodium for oro-trans soft-palatal delivery. The drug combination provides rapid and sustained therapeutic effects for migraine management. Methodology: Bio-flexible films were prepared by solvent casting using hydroxypropyl methylcellulose (HPMC E15), HPMC K100, and glycerine. A Box–Behnken Design was employed to optimize the formulation by evaluating three independent variables and five dependent responses. Films were characterized for thickness, surface pH, folding endurance, disintegration time, swelling index, drug content, ex vivo permeation, and in vitro drug release. Drug release kinetics were analyzed using mathematical models. Results and Discussion: All formulations exhibited satisfactory physicochemical and mechanical properties. The optimized formulation showed a disintegration time of 153 s, with cumulative drug release of 96.33% for Sumatriptan Succinate and 94.00% for Naproxen Sodium within 40 min. The optimized film demonstrated adequate mechanical strength, uniform drug content, acceptable swelling behavior, and enhanced ex vivo permeation. Drug release followed the Higuchi and Korsmeyer–Peppas models. Conclusion: The optimized bio-flexible mucoadhesive film demonstrated rapid drug release and efficient ex vivo permeation, indicating its potential as a patient-friendly platform for oro-trans soft palatal delivery of Sumatriptan Succinate and Naproxen Sodium. Further in vivo studies are required to confirm its clinical potential.

Simultaneous RP-HPLC quantification of curcumin, silymarin, and piperine: Method development and validation

2026-01-17T06:23:39+00:00

Background: Herbal formulations containing multiple phytoconstituents require analytical methods that can simultaneously determine structurally diverse compounds with adequate selectivity and precision. Curcumin (CUR), Silymarin (SLY), and Piperine (PIP) are widely incorporated into polyherbal preparations owing to their clinically studied pharmacological actions. Ensuring consistent quality of such formulations requires a validated, reliable chromatographic procedure. Methodology: A reverse-phase HPLC method was established for concurrent estimation of CUR, SLY, and PIP using an Agilent Zorbax Bonus RP column (250 × 4.6 mm, 5 μm). Separation was achieved with a mobile phase of 0.1% perchloric acid and acetonitrile (45:55, v/v) at 1.0 mL/min, with UV detection at 215 nm. The method was evaluated for specificity, precision, linearity, accuracy, and sensitivity using standard validation criteria aligned with internationally accepted analytical quality guidelines. Results and Discussion: The analytes were successfully separated within 11 minutes, with retention times of 4.09 min for Silymarin, 7.39 min for Piperine, and 10.25 min for Curcumin. System precision demonstrated %RSD values below 0.21% for all analytes. Recovery values across 80–120% concentration levels were close to 100%, with %RSD <0.5%, reflecting excellent accuracy. Calibration curves exhibited strong linearity (R² = 0.999). The method demonstrated high sensitivity with LOD values below 2 µg/mL and LOQ values below 6 µg/mL for each compound. Both intra-day and inter-day evaluations showed %RSD <0.4%, confirming robust reproducibility. Robustness testing with small, deliberate variations showed %RSD <1.5%, confirming the method's reliability. Conclusion: The developed RP-HPLC protocol offers a selective, reproducible, and sensitive analytical approach suitable for simultaneous quantification of SLY, PIP, and CUR in combined herbal matrices.

Optimization and evaluation of sirolimus nanodispersion drug-layered prednisolone tablets for the management of thrombocytopenia

2026-03-25T12:26:16+00:00

Background: Thrombocytopenia is a hematological disorder characterized by a reduced platelet count, increasing the risk of bleeding and impairing hemostasis. The present study aimed to develop and optimize a fixed-dose combination tablet comprising a sirolimus nanodispersion layered onto a prednisolone core tablet using a Box–Behnken experimental design as a potential therapeutic strategy for thrombocytopenia. Methodology: Sirolimus nanodispersion drug-layered tablets were prepared and optimized using a three-factor, three-level Box–Behnken design. The optimized formulation was evaluated for critical quality attributes, including hardness and friability, and subsequently experimentally validated. Therapeutic efficacy was investigated in cyclophosphamide-induced thrombocytopenic Wistar rats by assessing platelet count, bleeding time, clotting time, and hematological parameters, including red blood cell count, hemoglobin, and hematocrit. Results and Discussion: The optimized formulation exhibited acceptable mechanical properties, with hardness ranging from 5.3 to 5.5 kg/cm² and friability below 1%, confirming the robustness of the optimization process. In vivo evaluation demonstrated a marked improvement in platelet recovery following treatment. The platelet count increased from 39.87 ± 8.82 × 10³/mm³ in the disease control group to 132.62 ± 21.76 × 10³/mm³ and 154.57 ± 7.40 × 10³/mm³ after once-daily and twice-daily administration, respectively. Furthermore, treatment significantly improved bleeding time, clotting time, and hematological parameters, indicating enhanced therapeutic efficacy. Conclusion: The optimized sirolimus nanodispersion drug-layered prednisolone tablet demonstrated favorable pharmaceutical characteristics and significant therapeutic efficacy in the cyclophosphamide-induced thrombocytopenia model. The developed fixed-dose combination represents a promising formulation strategy for improving the management of thrombocytopenia and warrants further preclinical and clinical investigation.