We report a modified bicomponent solid-state form of tadalafil (TDF) and finasteride (FNS), prepared at a 1:1 molar stoichiometric ratio, corresponding to the USFDA-approved combination marketed under the trade name Entadfi, for the treatment of benign prostatic hyperplasia. Individually, both constituent drugs suffer from the limitation of low aqueous solubility, belonging to class-II of the biopharmaceutical classification system. A drug-drug coamorphous system of TDF and FNS was prepared by mechanochemical synthesis. Characterization of this novel phase was carried out by powder X-ray diffraction, thermal analysis, and FT-IR spectroscopy. Particle characteristics and morphological features of the coamorphous system were studied by scanning electron microscopy and 3D-laser scanning microscopy. Possible intermolecular interactions between TDF and FNS, facilitating the formation of the coamorphous phase, as indicated by spectroscopic analysis, were validated by the computational study employing density functional theory. Interestingly, in vitro dissolution studies showcased significant improvement in the dissolution profile of the coamorphous system compared with the physical mixture, which was successfully translated to the in vivo study in SD rats. Physical stability of the developed coamorphous system evaluated under accelerated as well as long-term stability conditions indicated reasonable stability for potential drug product usage. Considering its industrial applicability due to obvious benefits, viz., single solid phase, improved solubility, dissolution, and better pharmacokinetic parameters leading to higher bioavailability, the developed coamorphous system could prove to be a better therapeutic alternative over the marketed physical mixture.

Background: This work aimed to enhance the solubility of Tadalafil (TDL), a BCS Class II drug, by preparing Type IV lipid-based formulations. Methods: Type IV formulations were prepared using surfactants and/or hydrophilic co-surfactants, resulting in oil-free systems. Results: Based on the solubility test, Transcutol® HP exhibited the highest solubility for TDL (48.33 ± 0.004 mg/mL) and was selected as the co-surfactant. Among surfactants, Kolliphor® PS80 (42.74 ± 2.29 mg/mL), Kolliphor® EL (41.87 ± 2.50 mg/mL), Kollisolv® PEG 400 (40.70 ± 0.30 mg/mL), and Kolliphor® HS15 (31.40 ± 3.63 mg/mL) demonstrated high solubilization capacity. These were used to prepare formulations without the addition of an oil phase. The developed formulations resulted in a system with a nano-droplet size (<50 nm) and PDI values < 0.3, which was clear, transparent, and resistant to pH dilutions. The optimum Type IV lipid formulations were further characterized and demonstrated good thermodynamic stability under temperature and pH changes. The optimized formulation was adsorbed onto different carriers and transformed into solid TDL-loaded formulations. The in vitro dissolution rate of the drug from the solidified lipid formulations was studied in various dissolution media. It was observed that the solid formulations prepared with Neusilin US2® (2:1) exhibited a significantly higher dissolution of over 95% within 5 min compared to the marketed product. The in vitro lipolysis studies demonstrated that F2 formulation maintained TDL in a supersaturated state throughout digestion, with limited enzymatic degradation of the excipients. Cytotoxicity evaluation using the MTT assay in Caco-2 cells confirmed the biocompatibility of both drug-free and TDL-loaded formulations, with IC50 values of 19.55 µg/mL and 17.55 µg/mL, respectively. Conclusions: The overall results suggested that the developed solid Type IV lipid formulations can improve the dissolution rate of TDL, which would potentially lead to an improvement in its oral bioavailability and, consequently, a reduction in the treatment dose as a safe delivery system.

Pulmonary arterial hypertension (PAH) is a progressive disorder characterized by increased pressure in the pulmonary arteries, frequently resulting in right ventricular hypertrophy and heart failure. Phosphodiesterase type 5 (PDE5) inhibitors, such as sildenafil (SIL), tadalafil (TAD), and avanafil (AVA), have demonstrated efficacy in the treatment of pulmonary arterial hypertension (PAH). The growing interest in natural compounds, like usnic acid (UA), a dibenzofuran derived from lichens, stems from their promising potential as complementary therapies in various medical conditions. This study investigates the potential of UA as a PDE5 inhibitor compared to SIL, TAD, and AVA through ADMET analysis, molecular docking, and molecular dynamic simulations. The ADMET analysis suggests significant plasma protein binding and an extended half-life for UA, perhaps improving retention relative to synthetic inhibitors. Molecular docking analyses indicate that UA establishes stable interactions with PDE5, exhibiting binding energies similar to those of synthetic inhibitors. Molecular dynamic simulations validate the stability of these interactions and suggest that UA reduces the flexibility of PDE5, enhancing its inhibitory potential. The results demonstrate that UA may have a potential synergistic effect with PDE5 inhibitors in treating PAH, offering a favorable toxicity profile, particularly regarding cardiotoxicity and neurotoxicity.

The primary aim of this study is to detect and quantify the presence of Sildenafil (SDF) and Tadalafil (TDF) in dietary supplements marketed as natural sexual enhancers in Bosnia and Herzegovina. Additionally, the study seeks to utilize these findings to inform relevant authorities, enabling further testing in reference laboratories and prompting the necessary actions to remove these adulterated products from the market. Using high-performance liquid chromatography with diode array detection (HPLC-DAD), 20 samples were analysed for the PDE-5 inhibitors. The analysis revealed that seven of the samples contained either SDF or TDF, with mean concentrations ± standard deviation (SD) ranging from 2,075.57 ± 0.47 µg/g to 33,808.857 ± 99.43 µg/g, and TDF concentrations ranging from 24.16 ± 0.11 µg/g to 3,994.66 ± 6.95 µg/g. These findings indicate a significant health risk posed by the adulteration of these products. The widespread presence of these active pharmaceutical ingredients (APIs) in products falsely labelled as natural underscores the urgent need for stringent regulatory oversight and enhanced quality control measures to protect consumer safety. This study adds to the growing body of evidence concerning the adulteration of dietary supplements and emphasizes the critical importance of regulatory compliance and monitoring in safeguarding public health.

Tailored transethosomal systems for tadalafil transdermal delivery: Impact of Phosal and edge activators on skin permeation and cellular uptake

BackgroundPulmonary arterial hypertension (PAH) is a progressive disease characterized by endothelial dysfunction and inflammation. This study aimed to evaluate the effects of cilomilast (CIL), a phosphodiesterase-4 inhibitor, and tadalafil (TAD), a phosphodiesterase-5 inhibitor, on PAH induced by monocrotaline (MCT) in rats.MethodsForty Wistar albino rats were divided into five groups: control, MCT, MCT + CIL, MCT + TAD, and MCT + CIL + TAD. PAH was induced via MCT, and treatments were administered orally from days 21 to 35. Hemodynamic parameters, right ventricular pressure (RVP), echocardiographic findings, and histopathological lung and heart tissue changes were assessed. Nitric oxide (NO) levels in lung tissue were also measured.ResultsTissue NO levels were significantly greater in the MCT + CIL + TAD group than in the MCT group (p = 0.01). The RVP was lower in the MCT + TAD and MCT + CIL + TAD groups than in the MCT group (p < 0.05) but not in the MCT + CIL group. Histopathologically, lung perivascular infiltration and pulmonary artery wall thickness were significantly reduced in the MCT + CIL + TAD group, indicating an anti-inflammatory effect. However, CIL alone did not significantly impact pulmonary artery thickening or RVP.ConclusionCIL alone had no significant effect on PAH progression, but its combination with TAD improved inflammation scores and NO levels. These findings suggest that targeting inflammation alongside vasodilation may offer therapeutic benefits in PAH. Further studies with different doses and PAH models are recommended.

Objective: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and the accumulation of amyloid-beta (Aβ) peptides. The neuroprotective protein sestrin-2 (SESN2) has been implicated in the cellular response to oxidative stress and autophagy, processes that are disrupted in AD. This study explores the effects of phosphodiesterase inhibitors (PDEIs) roflumilast (RF), rolipram (ROL), and tadalafil (TAD) on SESN2 expression and autophagy in Aβ25-35-treated hippocampal neuron (HT-22) cell cultures.Methods: The HT-22 cells were exposed to 5 μM Aβ25-35 for 32 hours to induce AD-like pathology. Concurrently, cells were treated with PDEIs (ROL: 10 μM, TAD: 1.53 nM, RF: 5 μM). The SESN2, autophagy-related proteins (ATG5, beclin-1 (BECN1), LC3II), adenosine monophosphate-activated protein kinase (AMPK), and mTOR expression levels were analyzed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot techniques.Results: The Aβ25-35 exposure significantly increased SESN2 expression and altered the levels of autophagy-related proteins, resulting in decreased active AMPK (phosphorylated (p)-AMPK) and increased active mTOR (phosphorylated (p)-mTOR). Treatment with PDEIs reduced the elevated SESN2 expression and modulated autophagy-related protein levels, enhancing ATG5, BECN1, and LC3II expression. The PDEIs also restored p-AMPK levels and reduced p-mTOR expression in Aβ25-35-treated cells.Conclusion: The PDEIs exhibit neuroprotective effects in an in vitro AD model by reducing SESN2 overexpression and modulating autophagy through the AMPK/mTOR pathway. These findings suggest that PDEIs could be potential therapeutic agents for AD, targeting SESN2 and autophagy pathways to mitigate neurodegenerative damage.

The goal of the current research was to identify a safe and effective non-oncology drug combination as a substitute to existing toxic chemotherapeutics for the treatment melanoma. Further intend was to develop an oral solid self-emulsifying drug delivery system (S-SEDDS) for concurrent delivery of identified combination. The drug containing S-SEDDS was prepared and characterized for flowability, compressibility, drug content, particle size and zeta potential, and in vitro cytotoxicity against melanoma cells. In silico molecular docking for drug with excipients interaction shows compatibility with each other. Moreover, the formulations were characterized in vivo for hepatotoxicity and pharmacokinetic study in rats. The S-SEDDS showed good flowability and compressibility. The particle size of S-SEDDS upon dilution was found in nanometer range. Furthermore, the in vitro cytotoxicity of S-SEDDS containing non-oncology drug (NOD) combination [ketoconazole (KCZ), tadalafil (TLF), disulfiram (DSR)] and docetaxel (DTX) was observed to be higher than S-SEDDS containing only NOD combination against mouse melanoma cells. No significant change in the hematological parameters, animal vital organs weights, and body weights were observed after oral administration of S SEDDS containing non-oncology drug combination with DTX indicating their safety. In addition, significant (p&lt; 0.05) improvement in the oral bioavailability of DTX was observed following its administration in the form of S-SEDDS when compared to the Taxotere in the rats. The developed S-SEDDS containing non-oncology drug combination alone and in combination with docetaxel could be a promising and safe approach in the effective treatment of melanoma.

Method Development and Method Validation using RP-HPLC Method For Metformin Hydrochloride (MET), Tadalafil (TAL) In Rat Plasma-Application to The Pharmacokinetic Studies, Metformin hydrochloride (MET) is an oral anti-diabetic drug in the biguanide class for the treatment of type 2 diabetes mellitus. Tadalafil (TAL) is a medication used to treat erectile dysfunction and other conditions. For the pharmacokinetic study of MET and TAL, and we developed a simple and sensitive method for estimating MET and TAL in rat plasma using reverse phase high-performance liquid chromatography (RP-HPLC). The drug samples were extracted using solid phase extraction with a stationary-phase strata-X Cartridges and a 1ml mixture of mobile phase. Chromatographic separation was accomplished on a C18 column using (0.3) Triethyl anime buffer: methanol: acetonitrile (70:05:25 v/v) as mobile phase at a flow rate of 1ml/min and UV detection at 224nm. The retention time of MET. The TAL values were found respectively, with a 15-minute separation time. The developed method underwent validation for accuracy, precision, linearity, and recovery. Linearity studies were found to be acceptable between 0.4 and 6.4 ug/ml. The method was successfully applied to analyze rat plasma samples for pharmacokinetic studies, drug interactions, bioavailability, and bioequivalence.

The combination therapy of mirabegron (MIR) and tadalafil (TAD) has gained significant attention in clinical practice for the treatment of Benign Prostatic Hyperplasia as well as overactive bladder syndrome. This study demonstrates the development and validation of two analytical methods for the concurrent determination of tadalafil and mirabegron in their synergistic combo therapy. Spectrophotometry and stability-indicating HPLC were employed for the accurate quantification of both drugs. The spectrophotometric methods were based on derivative, Fourier and ratio derivative of the two drugs, providing simpler, rapid alternatives for routine analysis. The stability-indicating HPLC method was developed using a reverse-phase column with a methanol-phosphate buffer gradient mobile phase, achieving optimal separation with detection at 250 nm for MIR and 225 nm for TAD. Forced degradation studies were performed under acidic, basic, oxidative, neutral, thermal, and photolytic conditions, confirming the method’s ability to quantify MIR and TAD in presence of degradation products and establish drug stability. Both techniques were validated based on ICH guidelines, demonstrating excellent linearity, precision, accuracy, and sensitivity. The methods were successfully applied to the analysis of bulk powder and in dosage forms. Both methods were evaluated and found to be environmentally friendly, receiving approval as “green” according to the AGREE (Assessment Tool for Greenness) method, “white” under the RGB12 criteria, and “blue” according to the BAGI (Blue Analytical Greenness Index). These evaluations demonstrate the sustainability and eco-friendliness of the proposed analytical techniques. Furthermore, artificial intelligence was employed through an online tool to ensure that there were no potential drug-drug interactions between MIR and TAD, offering an additional layer of safety in clinical applications. This research contributes to the enhancement of quality control for patients undergoing combination therapy with MIR and TAD and stability testing.Graphical

Tadalafil (TDL) is a drug clinically proven to treat erectile dysfunction, benign prostatic hyperplasia, and pulmonary hypertension. TDL is classified as a BCS Class II drug, which means it has high permeability but low solubility. Solubility enhancement is achieved through the inclusion complex method and verified by dissolution testing. This study aims to determine the dissolution profile of tadalafil inclusion complex tablets using the β-cyclodextrin (βCD) inclusion complex method with disintegrant variations. The results show that the tablet hardness is: R1 = 6.6 ± 0.5 kgf, R2 = 6.48 ± 1.4 kgf, and R3 = 6.6 ± 1.3 kgf. The disintegration time evaluation shows: R1 = 4.66 ± 1.08 minutes, R2 = 5.08 ± 0.91 minutes, and R3 = 5.1 ± 1.1 minutes. Each formulation's tensile strength test results are: R1 = 1.3 MPa, R2 = 1.3 MPa, and R3 = 1.1 MPa. The average drug content in the inclusion complex tablets is: R1 = 104.11 ± 1%, R2 = 106.23 ± 0.1%, and R3 = 105.09 ± 1.9%. The dissolution profile of the inclusion complex tablets at the 30-minute mark is: R1 = 85.2 ± 4.2%, R2 = 79.7 ± 3.6%, and R3 = 77.4 ± 5.3%. Variations in disintegrants significantly affect the dissolution profile during the early minutes, which impacts the overall dissolution profile. The TDL-βCD inclusion complex method successfully achieved the Q value by the monograph specifications.

Antidepressant drugs, particularly selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are known to induce sexual dysfunction as a side effect. Duloxetine (DLX) and Tadalafil (TDL) are simultaneously determined in their pure state and laboratory-prepared mixtures by two novel, environmentally friendly, and accurate spectrophotometric methods. The first method based on second order derivatives while the second method is based on first derivative dual-wavelength detection. In method I, the linearity range was found to be 0.5–9 μg/mL and 1–14 μg/mL with limit of detection 0.15 μg/mL and 0.23 μg/mL for DLX and TDL, respectively, with a good correlation coefficient of 9998. In method II, the linearity range was found to be 1–10 μg/mL and 1–12 μg/mL with limit of detection 0.25 μg/mL and 0.20 μg/mL for DLX and TDL, respectively, with a good correlation coefficient of 0.9997 for DLX and 0.9998 for TDL. The validation of these methods followed the guidelines set by the International Council for Harmonization (ICH). The methods are accurate and precise. The proposed methods can be used for simultaneous determination of DLX and TDL in synthetic mixture. Additionally, the suggested method's greenness was assessed by means of four up-to-date ecological tools, namely the Eco-Scale, the National Environmental Method Index (NEMI), the Green Analytical Procedure Index (GAPI), and the Analytical Greenness metric approach and software (AGREE). The sustainability characteristics of the proposed method were also assessed using the Blue Applicability Grade Index (BAGI), a recently developed metric for assessing the practicality (blueness) of procedures.

Background/Objectives: Raynaud's phenomenon (RP) is characterized by an exaggerated vasoconstrictive response of small blood vessels in the fingers and toes to cold or stress. Oral therapy with tadalafil (TDL), a phosphodiesterase-5 inhibitor, is limited by systemic side effects and reduced patient compliance. This study aimed to develop and evaluate a TDL-loaded nanoemulgel for transdermal delivery as a non-invasive treatment alternative for cold-induced vasoconstriction. Methods: TDL-loaded nanoemulsions were prepared using the aqueous titration method with cinnamon oil as the oil phase and Cremophor RH40 and Transcutol as the surfactant-cosurfactant system. The optimized nanoemulsion was incorporated into a carbopol-based gel to form a nanoemulgel. The formulation was characterized for droplet size, morphology, thermodynamic stability, rheological properties, in vitro drug release, skin permeation, and pharmacokinetic behavior. Infrared thermography was employed to assess in vivo efficacy in cold-induced vasoconstriction models. Results: The optimized TDL nanoemulsion exhibited a spherical morphology, a nanoscale droplet size, and an enhanced transdermal flux. The resulting nanoemulgel displayed suitable physicochemical and rheological properties for topical application, a short lag time (0.7 h), and a high permeability coefficient (Kp = 3.59 × 10-2 cm/h). Thermal imaging showed significant vasodilation comparable to standard 0.2% nitroglycerin ointment. Pharmacokinetic studies indicated improved transdermal absorption with a higher Cmax (2.13 µg/mL), a prolonged half-life (t1/2 = 16.12 h), and an increased AUC0-24 compared to an oral nanosuspension (p < 0.001). Conclusions: The developed TDL nanoemulgel demonstrated effective transdermal delivery and significant potential as a patient-friendly therapeutic approach for Raynaud's phenomenon, offering an alternative to conventional oral therapy.

Erectile dysfunction (ED) and premature ejaculation (PE) are two common male sexual disorders encountered by clinicians daily. The first-line recommended treatment for ED is the use of phosphodiesterase type 5 (PDE5) inhibitors including Tadalafil (TADA). Dapoxetine (DAPO) has been approved in many countries as an on-demand treatment for PE, but the bitter flavor taste of oral Dapoxetine formulations is a commonly experienced issue. As a result, the taste of Dapoxetine has been effectively masked through encapsulation by Eudragit E100 using a spray-drying method. Production yield and encapsulation efficiency were 77.36%, and 99.03% respectively. The combination of Tadalafil and Dapoxetine are sold in the market as regular tablets. At present, there are no ODTs in the market that contain both Tadalafil and Dapoxetine. This study's goal was to create and describe orally disintegrating tablets (ODTs) that include Tadalafil and Dapoxetine. The ODTs were made through freeze-drying methods and direct compression techniques. Quality controls were conducted. ODTs made using direct compression and freeze-dried methods disintegrated in 62 and 29 sec, respectively. The in vitro dissolution test demonstrated that Tadalafil released from ODTs prepared by freeze-drying occurred more rapidly than from those made by direct compression. Conversely, Dapoxetine released more quickly from ODTs prepared by direct compression compared to those made by freeze-drying. This difference is attributed to the encapsulation of Dapoxetine using Eudragit E100 through spray drying for taste masking. 8.94% of Dapoxetine was released in the phosphate buffer pH 6.8 during the simplified dissolution test from ODTs prepared by freeze-drying in the first three minutes.

The current work aimed to design a new patient-friendly Tadalafil (TDL) oral spray for management of erectile dysfunction employing concept of advanced data mining and analytical tools. An inclusion complex of TDL: Dexolve®, was formulated and characterized for its physicochemical properties. Phase solubility study suggested a 1:1 ratio of TDL: Dexolve® showed higher solubility. FTIR, DSC, and XRD studies confirmed the partial alteration of crystalline to amorphous. The complex assessed in-vivo for taste masking inculcating the Brief Access Taste Aversion (BATA) model, indicated the taste masking of TDL. The complex was incorporated into spray formulation using water: ethanol, Vitamin D and HPMC E5. MLRA and ANOVA depicted the crucial correlation between amount of ethanol and HPMC E5 with spray pattern and % TDL release. The results of characterization suggested that it covered the maximum area of the oral cavity, indicated uniform distribution and more absorption. The design batches were evaluated for varied oral spray-related parameters and stability studies. The formulation was found stable and released TDL immediately. Dexolve® was found to be a promising multifunctional excipient. The oral spray prepared was environmentally friendly as it is propellant-free. The newer stable and immediateacting spray improves release of TDL and is patient-friendly.

A serious challenge of the chronic administration of dexamethasone (DEX) is a delay in wound healing. Thus, this study aimed to investigate the potential of Tadalafil (TAD)-loaded proniosomal gel to accelerate the healing process of skin wounds in DEX-challenged rabbits. Skin wounds were induced in 48 rabbits of 4 groups (n = 12 per group) and skin wounds were treated by sterile saline (control), TAD-loaded proniosomal gel topically on skin wound, DEX-injected rabbits, and DEX+TAD-loaded proniosomal gel for 4 weeks. The optical photography, transmission electron microscopy, in vitro release profile, and stability studies revealed the successful preparation of the selected formula with good stability. DEX administration was associated with uncontrolled oxido-inflammatory reactions, suppression in immune response in skin wounds, and consequently failure in the healing process. TAD-loaded proniosomal gel-treated rabbits manifested a marked enhancement in the rate of wound closure than control and DEX groups (p < 0.05). The TAD-loaded proniosomal gel successfully antagonized the impacts of DEX by dampening MDA production, and enhancing total antioxidant capacity, coupled with modulation of inflammatory-related genes, inducible nitric oxide synthase, tumor necrosis factor-alpha, interleukin-1β, and matrix metalloproteinase 9, during all healing stages (p < 0.05). This was in combination with significant amplification of immune response-related genes, CD68 and CD163 (p < 0.05). Moreover, the histopathological, Masson's Trichrome-stain, and immune-histochemical studies indicated a successful tissue recovery with the formation of new blood vessels in groups treated with TAD-loaded proniosomal gel, as manifested by well-organized collagen fibers, upregulation of transforming growth factor β1, and vascular endothelial growth factor immune expression in skin tissues (p < 0.05). Overall, the topical application of TAD-loaded proniosomal gel is useful in improving the delayed wound healing linked to DEX therapy via regulating the release of inflammatory/macrophage activation mediators and enhanced antioxidant capacity, angiogenesis, and vascularity.

To investigate the clinical efficacy of moxibustion (Mox) combined with low-dose tadalafil (TAD) in the treatment of diabetes mellitus-induced erectile dysfunction (DMED) with the syndrome of Qi deficiency and blood stasis. According to the inclusion and exclusion criteria, we selected 90 patients with DMED for this trial and equally randomized them into a Mox, a TAD, and a Mox combined with TAD (Mox+TAD) group to be treated by mild Mox applied to the acupoints Zusanli, Sanyinjiao and Yinlingquan qd alt, oral medication with low-dose TAD at 5 mg per dose qd, and combination of the above two therapies, respectively, all for 4 weeks. We obtained from the patients their IIEF-5 scores, traditional Chinese medicine (TCM) symptoms scores, Erectile Hardness Scale (EHS) scores, corpus cavernosal hemodynamic indexes, and the peak systolic velocity (PSV), end diastolic velocity (EDV) and resistance index (RI) of the corpus cavernosal arteries before and after treatment, and compared them among the three groups. The total effectiveness rate was significantly higher in the Mox+TAD (90.0%) than in the Mox (46.7%) and TAD groups (60.0%) (P< 0.05). Compared with the baseline, the IIEF-5 and EHS scores were increased, while the TCM symptoms scores decreased in all the three groups after treatment, more significantly in the Mox+TAD group than in the other two (P< 0.05). And the PSV and RI were remarkably increased, while the EDV decreased (P< 0.05) in all the three groups (P< 0.05) after treatment, with PSV even higher in the Mox+TAD than in the Mox and TAD groups (P< 0.05). Moxibustion combined with tadalafil has a definite efficacy and safety for the treatment of DMED, which can effectively improve the erectile function of the patients by increasing penile blood supply, benefiting qi and activating blood circulation.

In 2019, 94.00 million prevalent cases of benign prostatic hyperplasia (BPH) were reported, accounting for 2.48% of the global population. BPH is a significant urological health concern worldwide, leading to considerable economic burdens. The European and American guidelines for lower urinary tract symptoms were recently updated in 2023/2024, supporting a combination therapy of alpha-1 blockers with phosphodiesterase-5 inhibitors. Moreover, patents describing this combination have been previously reported. In this work, a novel, totally green organic-solvent-free mixed-micellar liquid chromatography method was developed to simultaneously analyze alpha-1 blockers alfuzosin (ALF) and tamsulosin (TMS) and phosphodiesterase-5 inhibitor tadalafil (TAD). Response surface methodology was employed to optimize the critical chromatographic variables, and a design space representing the robustness zone was identified. Separation was achieved on an RP-C18 column (150 × 4.6 mm2, 5 μm) using a green mixture of Brij-35 (19.91 mM), SDS (130.00 mM), and sodium dihydrogen phosphate buffer (10.00 mM) at pH 4.65. The flow rate was set at 1.5 mL min-1, and UV detection was observed at 250, 285 and 214 nm for ALF, TAD and TMS, respectively. The method was validated over a concentration range of 5-100 μg mL-1 for all drugs with detection limits of 0.77, 1.23 and 1.59 μg mL-1 and quantification limits of 2.35, 3.73 and 4.82 μg mL-1 for ALF, TAD and TMS, respectively. The method was applied to determine the content of the analytes in various tablets and other pharmaceutical products. Greenness of the method was assessed using the Analytical GREEnness metric approach (AGREE), and the blueness was assessed using blue applicability grade index (BAGI), with scores of 0.76 and 82.5, respectively. These scores underline the superiority of the proposed procedure over previously reported methods.

To investigate whether tadalafil (TAD) and N-acetyl cysteine (NAC) can prevent cisplatin (CIS)-induced testicular toxicity. Forty Wistar-Albino rats were divided into five groups: Control group, CIS group, TAD group, NAC group and TAD + NAC group. All groups were compared regarding body and testicular weights, testicular volumes, blood testosterone levels, testicular tissue malondialdehyde (MDA) levels, histopathological features, and testicular Cosentino and Johnsen scores. There was no significant difference between the groups regarding body weights and Johnsen scores. It was observed that TAD and NAC affected the apoptotic index, and Cosentino scores were lower in these groups than in the control group. This effect was most prominent in the TAD + NAC group. The CIS treatment led to a decrease in serum testosterone levels. While testosterone levels were higher in the TAD Group, no statistically significant difference was found between the groups. Combination therapy and NAC did not affect blood testosterone levels. Cisplatin has adverse effects on the testicular tissue. The histopathological changes caused by this agent can be prevented by TAD + NAC combination therapy.

Background: obesity enhances a chronic inflammation and oxidative stress and damages the vascular endothelium. Tadalafil restores signaling of NO signaling and may decrease circulating oxidative stress and markers of inflammation, and improves parameters of metabolism through a number of mechanisms. The aim of this study to show what the effects of the administration of tadalafil (TAD) on inflammation, and oxidative stress markers in obese male patients. Methods: 32 male subjects with BMI more than 23 and age range 30-50 years old underwent with TAD 5mg for 14 days .Plasma level of MDA , GsH ,IL-6 and Hs-CRP before the taking of drugs and after 14 days of treatment . Results: Treatment with TAD caused a non-significant reduction in MDA group (0.093±0.027 versus 0.082± 0.032, P- value is 0.196), a non-significant increase in plasma GsH (0.1074±0.007 versus 0.109±0.009 , p-value is 0.538), a non-significant of reduction in plasma level of plasma Hs-CRP and IL-6 (4.377± 0.702 versus 4.272± 0.693, p-value is 0.599) and (24.668± 6.001 versus 23.56± 2.587 ,p-value is 0.401)respectively . Conclusion: We have concluded that TAD therapy has non –significant effect on anti-inflammatory and anti-oxidant activity if used in short term but this effect may be significant if used for long term or use large dose