This research aimed to develop hydrogel formulations incorporating carvacrol-(3-cyclodextrin inclusion complexes to overcome carvacrol's inherent challenges: high volatility, chemical instability, and poor water solubility, while retaining antimicrobial properties. The study focused on characterizing formulations using different hydrophilic polymer matrices-carbomer and hydroxyethyl cellulose (HEC) while maintaining fixed carvacrol concentrations. Carvacrol-(3-cyclodextrin complexes were synthesized using co-precipitation methodology at 20:80 ratio, achieving enhanced solubility (0.005 g/ml) compared to free carvacrol. Four hydrogel variants were formulated: two carbomerbased (0.2%) and two HEC-based (3%), with select formulations containing or not chamomile essential oil as an additional active component that potentially contributes with anti-inflammatory benefits. Rheological evaluation demonstrated distinct viscosity profiles between polymer systems. Carbomer formulations showed significantly higher viscosity, indicating superior mechanical stability and extended residence time at application sites. Conversely, HEC formulations exhibited mucoadhesive properties, facilitating application and uniform distribution. These characteristics suggest carbomer systems favor applications requiring structural durability and controlled release, while HEC systems excel in mucoadhesive topical applications. All formulations maintained excellent homogeneity with physiological pH ranges (6.74-7.00), and were evaluated for antibacterial activity before and after incorporation into carbomer and hydroxyethyl cellulose (HEC) hydrogels. They exhibited strong, concentration-dependent antimicrobial activity against the target bacterial strains. A slight reduction in activity (2-3%) was observed post-formulation, confirming the successful release of essential oils from the hydrogel matrices. The integration of carvacrol-(3-cyclodextrin complexes into hydrophilic polymer matrices successfully addressed solubility limitations while maintaining stability. Both polymers proved suitable as hydrogel bases with distinct rheological profiles offering flexibility for different applications, opening new therapeutic possibilities for carvacrol in clinically relevant formulations.
The “French Paradox” describes an epidemiological association between resveratrol (RSV) consumption and reduced incidence of certain chronic diseases. However, consuming large amounts of wine for one epidemiological reason, would be inappropriate due to the alcohol toxicity. Since RSV has poor pharmacokinetics, this study aimed to synthesize novel RSV ester derivatives, elucidate their structures, and evaluate their in vitro toxicity and transmembrane prodrug potential. For that purpose, considering the carbonate anion which is not a foreigner to the body, RSV carbonate esters were designed and synthesized. Then, the toxicity, IC50 values, and phase-I metabolic stability of the synthesized compounds were tested. Finally, the transmembrane properties of RSV carbonate esters were tested through a Franz Cell study. The results demonstrated that esterification of RSV hydroxyl groups markedly reduced intrinsic biological activity, consistent with the expected behavior of prodrug forms. Among the synthesized derivatives, compound 2 exhibited favorable release properties; however, its excessive metabolic stability limited efficient conversion to RSV, reducing its suitability for further development, whereas the other derivative was identified as a promising candidate for subsequent studies.
The study aimed to evaluate and compare the performance of different ready-to-use excipients in the formulation of Deferasirox (DFX) orally disintegrating tablets (ODTs) using direct compression. Ready-to-use 150, Parteck (R) LUB MST were blended with Deferasirox. The blend consisting of eight different formulations was evaluated for powder properties, including angle of repose, bulk density, tapped density, Hausner's ratio, and compressibility index. The produced tablets were evaluated for tablet properties, including weight variation, breaking force, thickness, friability, disintegration test, and dissolution test. According to all the obtained results, none of the prepared formulations could fulfill the requirements needed to be applicable as an individual excipient of ODT. The formulations that could pass all the tests except the dissolution test were formulation (F5) Ludiflash (R) and formulation (F4) KollitabTM DC 87 L. Ludiflash (R) could provide a drug release after 30 minutes of (45.62%), which was more than KollitabTM DC 87 L, which provides (35.32%). These excipients cannot be used alone for ODTs. Further study is needed to optimize the formulations.
In this work, the amount of Ritlecitinib in rat plasma was determined using a liquid chromatography-tandem mass spectrometry approach. Crizotinib is an internal standard(IS). With a 3.5 & micro;m particle size and dimensions of 150 x 4.6 mm, the Waters X-Terra RP-18 column was used for the chromatographic separation. Acetonitrile: TEA pH-2.5/Formic acid in a 60:40% v/v ratio was used as the mobile phase at a flow rate of 1.0 mL/min. The drug and IS were extracted using the liquid-liquid extraction technique. Proton adducts of Ritlecitinib and Crizotinib were detected at m/z 286.159-105.7458 and 451.3378-282.4251, respectively, in the positive mode of multiple reaction monitoring (MRM). The validation was carried out within the linear concentration range of 12.50-100.0 ng/mL. The coefficient of variation (%CV) for Ritlecitinib was determined to be 2.80% and 96.47%. Further, the precision and accuracy results for HQC, MQC, LQC, and LLQC were determined to be 98.02%, 98.42%, 98.62%, and 96.13%. With this method the average recovery rate was found to be 98.78%.
This study examines the impact of mergers and acquisitions (M&A) on innovation and competitiveness within the pharmaceutical sector, a critical industry characterized by intensive R&D and dynamic market conditions. Using a panel dataset spanning multiple countries and years, relationships among key indicators such as R&D expenditure, patent applications, market share changes, and M&A activity are analyzed. Advanced econometric techniques, including panel regression models and Granger causality tests, are employed to explore both direct effects and temporal dynamics. The findings reveal a complex interplay between M&A activities and innovation outputs, highlighting bidirectional causality and contextual influences. By providing empirical evidence on the dual role of M&A as both an enabler and potential inhibitor of innovation, this research contributes to the ongoing discourse on sustainable growth strategies in the pharmaceutical sector. The study offers actionable insights for policymakers and stakeholders, emphasizing the importance of balancing innovation promotion with competitive dynamics.
This study developed and validated a robust UV spectrophotometric and RP-HPLC method for the simultaneous estimation of dapagliflozin and sitagliptin in tablets, adhering to ICH guidelines. UV analysis identified lambda max at 223 nm (dapagliflozin) and 267 nm (sitagliptin). The concentration ranges employed to assess linearity for dapagliflozin, and sitagliptin were 5-25 & micro;g/ml, and 25-125 & micro;g/ml, achieving linearity with R & sup2; > 0.999 and accurate recovery rates in range of 98-102%. Assay was found to be 106.4 for dapagliflozin and for 102.8 sitagliptin. RP-HPLC employed a Phenomenex Luna LC C18 (150mmX4.6mm,5 & micro;m) column with acetonitrile: methanol: water (25:35:40) as the mobile phase, at a flow rate of 1 ml/min. Detection was carried out at 215 nm retention time of dapagliflozin and sitagliptin was found to be 7.1 and 4.9 min. The method demonstrated linearity for dapagliflozin (4-20 & micro;g/ml) and sitagliptin (20-100 & micro;g/ml) with R & sup2; > 0.999, and %RSD < 2% for precision. The % recovery of spiked sample was 100% (dapagliflozin) and 98.5% (sitagliptin). Assay results for a marketed formulation revealed 90% and 104.3% of labelled amounts for dapagliflozin and sitagliptin, respectively, ensuring compliance with pharmaceutical standards. Both methods were precise, accurate, and robust, suitable for routine quality.
This study introduces a combined HPLC and UV detection technique for the quantification of casticin in capsule and human plasma samples. The chromatographic separation was carried out utilizing a C18 column (150 mm & times; 4.6 mm & times; 5 mu m) at a temperature of 25 degrees C. Isocratic elution with a mobile phase comprising 60:40 v/v (methanol-0.05% formic acid) was employed. Flow rate was adjusted 1 mL/min. The analyte was determined at a wavelength of 258 nm, with a retention time of 14.7 +/- 0.01 min. The developed method underwent validation according to ICH criteria, covering specificity, linearity, precision, accuracy, detection and quantitation limits, as well as robustness. The linear range was determined to be 10-60 ng/mL for both capsule and spiked plasma specimens. The suggested technique was performed to the analysis of casticin in spiked human plasma and pharmaceutical preparations, yielding a recovery of 106.04% and demonstrating precision through intra-day and inter-day experiments with the highest relative standard deviation (RSD %) value of 4.94. Consequently, the technique was performed to the quantifying of human plasma specimens from in a patient taking medication containing casticin.
This study investigated the effect of a newly synthesized original molecule with a 1,2,4-triazole with a 2-fluorophenyl ring on miRNA. (S)-Naproxen was chosen as the starting molecule for synthesis. In molecular modeling studies, compound (4a) was used to control for the Bcl-2 apoptotic marker. The primary objective was to demonstrate that the MDA-MB-231 cell line exhibited growth inhibition in a dose-dependent manner following compound treatment. The results showed that compound (4a) inhibited the motility of MDA-MB-231 cells. Compound (4a) at concentrations of 75, 150, and 300 & micro;M significantly reduced the viability of MDA-MB-231 cells compared to the control group. IC50 value of the compound (4a) for 48 h was 57.6 & micro;M. In our study, for the first time, miR-133a-5p was significantly up-regulated in MDA-MB-231 breast cancer cells treated with compound (4a) at different concentrations compared to the control group. As such, miR-133a-5p may play a crucial role in tumorigenesis by targeting Bcl-2 in MDA-MB-231 cells and could serve as a biomarker for therapeutic targets in breast cancer treatment.
Erodium pelargoniiflorum Boiss. & Heldr. belongs to the Geraniaceae family and an endemic species for Turkiye. Previous studies have demonstrated the aerial parts of Erodium pelargoniiflorum has been investigated for its alkaloid and phenolic acid contents by TLC methods and antispasmodic, cytotoxic and enzyme inhibitory activities. Nevertheless, none of the previous research has been done to identify the antioxidant potential and anti-urease activity and total phenolics of the root, flower and aerial parts of the plant. In this study, antioxidant and anti-urease activities of the root, flower and aerial parts extracts prepared with dichloromethane, ethyl acetate and methanol were investigated. The highest antioxidant potential was observed in the methanol extract of the flowers. The dichloromethane extract of the aerial parts showed the highest urease inhibition activity.
The Lamiaceae family comprises a large number of aromatic plant species with notable medicinal, culinary, and cosmetic applications. Within this family, the genus Thymus widely used in Turkish folk medicine. Thymus cilicicus, has been also used in traditional practices in the form of herbal teas, aromatic waters, and essential oils for the treatment of ailments such as toothache, stomach discomfort, respiratory disorders, diabetes, hypertension, and the common cold. Previous studies have reported antioxidant, antimicrobial, antidiabetic, cytotoxic, and acetylcholinesterase (AChE) inhibitory properties in T. cilicicus extracts obtained with organic solvents. These activities are mainly associated with the presence of phenolic compounds. However, existing literature has not yet addressed the biological activity and chemical composition of extracts obtained through traditional preparation methods such as infusion or maceration. Present study investigates antioxidant capacity such as 1,1-diphenyl-2-picrylhydrazyl radical scavenging (DPPH), ferric reducing antioxidant potency (FRAP) and cupric reducing antioxidant capacity (CUPRAC) along with AChE inhibitory activities of T. cilicicus extracts (ethanol maceration, water maceration, and infusion). Chemical profiles of the extracts were assessed via total phenolic content determination and LC-HRMS. LC-HRMS profiling of tested extracts revealed that major compounds of extracts were fumaric acid, p-coumaric acid, sinapinic acid, and, caffeic acid. Ethanol macerate extract exhibited higher total phenolic content and antioxidant activity in DPPH radical scavenging and CUPRAC assays compared to traditional preparation forms, while infusion extract exhibited highest activity in FRAP assay. None of the tested extract showed AChE inhibition at 100 µg/mL.
Enzymes involved in conversion of arachidonic acid into prostaglandins include Lipoxygenase and Cyclooxygenase, which play a crucial role in pro-inflammatory processes. Medicine that inhibit cyclooxygenase are classified as Nonsteroidal Anti-Inflammatory Drugs (NSAIDs), which exhibit significant anti-inflammatory properties, along with several adverse effects, particularly on the gastrointestinal mucosa, attributed to presence of various functional groups. Hence, present research work is designed to develop safer anti-inflammatory derivatives of naproxen that possess dual inhibition capabilities for both Cyclooxygenase and Lipoxygenase pathways, while also has safety profile. Four derivatives of Naproxen (NS9-NS12) were synthesized through a three-step process and were characterized by 1H NMR, 13C NMR, HR-ESI-MS techniques. Additionally, the safety profile was checked according to OECD guidelines 423 where a single dose of 2000 mg/kg (b.wt) of all derivatives was administered through oral route.The in vitro anti-inflammatory activity was assessed through the Lipoxygenase and Cyclooxygenase inhibitory pathways. Derivatives were found safe up to dose 2000 mg/kg (b.wt) having no mortality and behavioral changes in any animals derivatives treated group. In Cyclooxygenase pathway, NS12 and NS11 demonstrated high significant inhibitory effect against cyclooxygenase 2, with IC50 value of 1.0 mu M at concentration 1000-31.25 & micro;g/mL in contrast to COX-1 indicates as potent COX-2 inhibitor. While the IC50 for NS9 and NS10 was 74.0 and 24.0 mu M respectively on the same concentration. The IC50 for Celecoxib was 0.24 mu M at concentration 1000-31.25 & micro;g/ml. In Lipoxygenase pathway, NS11 exhibited an IC50 of <01 mu M, also within the concentration range of 1000-31.25 & micro;g/mL, with percent inhibition values of 91.23 +/- 0.48, 87.44 +/- 0.80, 85.72 +/- 0.61, 81.65 +/- 0.72, 77.86 +/- 0.38, 73.45 +/- 0.77. In comparison with Cyclooxygenase and Lipoxygenase activities, NS12 showed greater percent inhibition for Cyclooxygenase while for Lipoxygenase was NS11. From the docking conformation compound NS11 was found good docking score of -15.9737 formed four polar interactions, one pication and five pi-H linkages with the active residues of the lipoxygenase enzyme.
Ficus carica (fig) has been shown to possess properties that induce cell death, making it a potential anti-cancer agent; however, its mechanism of action remains largely unknown. This study aims to identify potential common apoptotic, necrotic, and autophagic gene expression changes following Ficus carica treatment in different tumor cell lines.Two different malignant cell lines (HT-29, MG-63) were used to examine the effects of F. carica extract on cell death pathway genes. The effect of the extract on cell viability was determined in our previous study using the MTT assay. Cells were treated with the F. carica extract according to the determined IC50 dose and time point. Apoptotic, necrotic, and autophagic gene expression changes were confirmed by qRT-PCR.F. carica treatment induced apoptosis, autophagy, and necrosis in different cell lines. Among the genes with the strongest regulation of cell death-related expression, we identified pro-apoptotic (Caspase-3, Bad), autophagic (LC3-II, Atg-5), and necrotic (RIP1, RIP3) transcription factors. These pathways were found to interact each other. The results indicate that F. carica activates different types of cell death in cancer cell lines without exhibiting cytotoxic effects on healthy cells.This study represents the first combined analysis of potential target genes in apoptosis, necrosis, and autophagy pathways following F. carica treatment across two different malignant cell lines. The findings demonstrate that F. carica is an effective anti-cancer agent capable of inducing various cell death pathways.
Urinary tract infection (UTI) and vaginitis are common conditions among females, significantly impacting overall life health and quality, imposing economical burdens and rising concerns of antibiotic resistance and limiting current treatments, probiotics have emerged as promising non antibiotic adjuvant and alternatives. Lactobacillus species restore and sustain a balanced microbiome offering protection against uro-pathogens by enhancement of epithelium barrier, immune modulation, competitive exclusions and biofilm disruptions. Clinical trials have documented the efficacy of probiotics both orally and vaginally in reducing UTI, preventing recurrences and restoring vaginal microbiota. This review highlights the aspects of probiotics mechanism of action, clinical trials and applications, exploring potentials of next generation probiotics and advancement in in delivery systems. While probiotics offer promising efficacy in managing UTI and vaginitis, further research studies are required to clarify exact mechanisms, strains potentials, dosage forms and doses, framing regulations regarding probiotics industry and tailored probiotics field.
In a world of high competition, expensive health care costs and the need for patient access to various biologic treatments lead to the development of biosimilars. Biosimilar is a biological product that has great similarity to a biologic drug which was taken as a reference having no clinical differences. Companies are eligible to manufacture them when the exclusive patent on the biological product has expired. They are approved according to the same standards of pharmaceutical quality. As they are comparatively cheaper than biological products, they have better reach among many patients. They are mainly targeted towards treating non-communicable diseases such as cancer, asthma, and arthritis. An alarming rise of cases of non-communicable diseases is being seen across various developing countries thereby increasing the value of biosimilars. Versavo is a classic example of a biosimilar product launched in India which is referenced from Roche’s Avastin which has shown its effectiveness in the treatment of various types of cancers. Even though biosimilars accomplish the same results as branded drugs, they have a different composition and their development period is longer than the generic drugs.
This study aimed to examine changes in physical and chemical properties, bioactive components, and antimicrobial and antioxidant activities in tamarillo fruit juice fermented by Lactobacillus plantarum. Tamarillo fruit juice was fermented for 96 hours. The total microbial, titrated acid and pH were tested during fermentation every 6 hours. Changes in color, viscosity, total phenolic, total flavonoid, anthocyanin, and antioxidant activity were tested at 0, 24, 72, and 96 hours. The results showed that L. plantarum could grow well on tamarillo fruit juice, which was characterized by an increase in the number of cells from 2.6 & times;107 CFU/mL (0 hours) to 7.3 & times;108 CFU/mL (24 hours) and 3.8 & times;1012 CFU/mL (96th hour). Fermentation of tamarillo fruit juice by L. plantarum caused a decrease in pH from 3.62 to 3.31 and increased total titrated acid from 1.58% to 2.49%. The antioxidant activity continued to decrease during fermentation. In contrast, the antimicrobial activity increased against Bacillus subtilis and Staphylococcus aureus. It can be concluded that the fermentation process causes changes in the physical, chemical, and bioactive components of tamarillo fruit extract and has an impact on reducing antioxidant activity but increasing antimicrobial activity.
Origanum species (oregano), which have been used as spices and medicines since ancient times and are one of the important riches of our country, are also known as important species in terms of the bioactive compounds they contain. In this study, phytochemical contents and biological activities of methanol extracts (OM & Idot;N, OSAM and OSOM) obtained from the aerial parts of three endemic Origanum species, Origanum minutiflorum, O. saccatum and O. solymicum, were comparatively analyzed. Extracts were obtained by maceration method. Antioxidant, anti-inflammatory and antidiabetic activities were evaluated using DPPH/ABTS radical scavenging, 5-lipoxygenase and alpha- glucosidase inhibition methods, respectively. Total phenol, flavonoid and triterpene contents were calculated by Folin-Ciocalteu, AlCl3 and Acetic acid/Vanillin/Perchloric acid methods, respectively. Phenolic compounds of the active extract were analyzed by HPLC. OSAM with IC50 values of 13.51 and 81.23 & micro;g/mL exhibited the strongest antioxidant activity against DPPH and ABTS radicals. OSAM with an IC50 value of 84.11 & micro;g/mL and OSOM with an IC50 value of 102.00 & micro;g/mL showed the best inhibitory activity against alpha-glucosidase and 5-lipoxygenase enzymes, respectively. Total phenol and flavonoid contents were highest in OSAM (132.30 and 60.32 mg/g) while total triterpene content was highest in OMIN (177.39 mg/g). In the HPLC analysis of the most active OSAM, rosmarinic acid as the major compound was detected in high amounts (211.061 mg/g extract). These results show that OSAM has a strong antioxidant and antidiabetic activity and that other phenolic acids and flavonoids, especially rosmarinic acid, may be responsible for these activities. However, in vivo studies are needed to be sure of the activities and bioactivity-directed fractionation method is required to reveal the compounds responsible for the activity.
Psoriasis is a chronic, inflammatory, and immune mediated dermatological diseases that adversely affects the quality of life of millions of individuals worldwide. Due to its heterogeneous nature, which varies from patient to patient, and its systemic manifestations, current treatment approaches are often insufficient and make disease management challenging. This complex pathophysiology has increasingly highlighted the need for more targeted and effective drug delivery systems beyond conventional therapeutic strategies. In recent years, nanotechnology-based drug delivery strategies have attracted attention in psoriasis treatment due to their potential to offer more effective pharmacodynamic profiles and reduce undesirable systemic effects. Among these, microemulsion systems are considered innovative delivery platforms thanks to their high stability, ability to penetrate biological barriers, and controlled release properties. Recent preclinical studies have demonstrated that these formulations can significantly enhance anti-inflammatory, immunomodulatory, and antiproliferative effects. This review aims to evaluate therapeutic potential, formulation techniques, pharmaceutical performance, and translational possibilities of microemulsion-based delivery systems considering preclinical and clinical studies published between 2019 and 2024.
Unintended pregnancy imposes a critical global health, social and economic burden. It was estimated about one-third of unintended pregnancies in Southeast Asia were due to low use of contraception, contraceptive method failure, and high unmet need for contraceptives. This study explored the current practices and issues in dispensing hormonal contraceptives in community pharmacy settings in Malaysia. An in-depth qualitative study using semi-structured interviews was conducted among the stakeholders consisting of community pharmacists, general practitioners, Obstetrics and Gynaecology (O&G) specialists, medical officers and pharmacists from the Ministry of Health. Eighteen participants were recruited using purposive sampling. The interviews were completed when saturation was achieved and analysed using an inductive approach to identify themes, whereby emerging themes were coded and grouped into categories. Three themes were identified: healthcare professional factors, consumer factors and system factors. Community pharmacists should anticipate challenges in dispensing contraceptives mainly attributable to a lack of training and guidelines or standardisation.
Orally disintegrating tablets (ODTs) improve patient compliance, but they present challenges in terms of masking the bitter taste of active pharmaceutical ingredients such as dexketoprofen trometamol (DEX). The study aimed to develop palatable DEX ODTs by granulating drug with Kollicoat MAE 30DP (R) to create a physical barrier. Using a quality by design (QbD) approach, an initial risk assessment identified Prosolv (R) ODT G2, Emdex (R), and Magnasweet (R) MM100 and tablet compression pressure as critical variables. A Box-Behnken design was employed to prepare 26 formulations, systematically evaluating the impact of these variables across low and high polymer concentrations. The results showed that although high concentrations of Kollicoat MAE 30DP initially delayed the dissolution rate, this barrier effect did not affect the final extent of drug release. Disintegration was predominantly governed by compression pressure, which altered tablet porosity, whereas PROSOLV (R) ODT G2 significantly influenced the overall dissolution profile. By optimizing the superdisintegrant-to-binder ratio, high-polymer formulations successfully overcame the initial retardation, consistently exceeding an 85% cumulative release at 30 minutes.
Human papillomavirus (HPV) is the most common sexually transmitted infection and a major cause of cervical and other cancers. This cross-sectional study aimed to assess university students' knowledge of HPV infection, testing, vaccination, and HPV-related cancers across different regions of T & uuml;rkiye. Data were collected from 1,856 students enrolled in associate, undergraduate, and postgraduate programs using a validated HPV Knowledge Scale. Statistical analyses included descriptive statistics, t-tests, ANOVA, and Pearson correlations. Overall, awareness of HPV (76.3%), HPV testing (70.1%), and HPV vaccination (77.5%) was relatively high, while only 11.3% of participants had been vaccinated. The mean total knowledge score was 13.19 +/- 8.64, indicating moderate knowledge. Higher scores were associated with female gender, higher education level, family history of cancer, and prior knowledge of sexually transmitted infections or cervical cancer (p<.05). Regional variations were observed, with the Aegean, Central Anatolia, and Marmara regions showing higher knowledge levels. A weak but significant positive correlation was found between age and knowledge (r=0.206, p<.001). The findings highlight persistent gaps in HPV vaccination and screening awareness among university students. Targeted educational interventions, particularly for male and non-health students, and national inclusion of HPV vaccination programs could strengthen preventive strategies against HPVrelated cancers.
