A Web-Based Survey of Patients Dispensed Viagra Connect® Behind the Counter in UK: An Evaluation of Effectiveness of Additional Risk Minimization Measures.

Purpose: A national additional risk minimization measures (aRMMs) program was implemented to train pharmacists for safe supply of non-prescription Viagra Connect® (VC) to erectile dysfunction (ED) patients in United Kingdom (UK). A survey aimed to evaluate the effectiveness of aRMMs. Methods: A cross-sectional, web-based survey enrolled ED patients who purchased at least 1 supply of VC in UK, using a structured self-administered questionnaire. Patients were assessed for the suitability of VC and received appropriate advice from pharmacists. Descriptive statistics were used. Results: The final sample had 297 patients, who reported that pharmacists inquired about blood pressure and heart comorbidities (91.9%), relevant illnesses (87.9%), medications (86.5%), ED diagnosis (82.2%), and were advised to consult their doctor regarding ED (51.2%). Furthermore, 85.5% of patients were advised on how to take VC correctly, 82.2% on possible side effects for which they might have to discontinue taking VC and consult their doctor, 80.1% on being informed that ED could be caused by underlying conditions. About 65.0% reported that they had visited (19.2%) or planned to visit (45.8%) their doctor. A majority (68.7%) also indicated that they had received advice on lifestyle modifications to manage their ED-related health risks. Conclusion: This survey provided a reasonable confirmation of the effectiveness of the VC aRMMs program and assurance that ED patients, when requesting and purchasing VC in UK pharmacies, are assessed appropriately for suitability of VC and receive the appropriate advice from pharmacists.

A national additional risk minimization measures (aRMMs) program was implemented to train pharmacists for safe supply of non-prescription VC to erectile dysfunction (ED) patients in United Kingdom (UK). A cross-sectional, web-based survey enrolled ED patients who purchased at least 1 supply of VC in UK, using a structured self-administered questionnaire. Patients were assessed for the suitability of VC and received appropriate advice from pharmacists. The final sample had 297 patients, who reported that pharmacists inquired about blood pressure and heart comorbidities, relevant illnesses, medications, ED diagnosis, and were advised to consult their doctor regarding ED. Additionally, most of the patients had consulted or planned to consult their doctors, on how to take VC correctly, on possible side effects for which they might have to discontinue taking VC and consult their doctor, on being informed that ED could be caused by underlying conditions, and on lifestyle modifications. A majority also indicated that they had received advice on lifestyle modifications to manage their ED-related health risks. This survey provided a reasonable confirmation of the effectiveness of the VC aRMMs program and assurance that ED patients, when requesting and purchasing VC in UK pharmacies, are assessed appropriately for suitability of VC and receive the appropriate advice from pharmacists.

Neurodevelopmental outcomes at 2 years in children who received sildenafil therapy in utero: The STRIDER randomised controlled trial.

OBJECTIVE: Severe early-onset fetal growth restriction (FGR) causes stillbirth, neonatal death and neurodevelopmental impairment. Poor maternal spiral artery remodelling maintains vasoactive responsiveness but is susceptible to treatment with sildenafil, a phosphodiesterase type 5 (PDE5) inhibitor, which may improve perinatal outcomes. DESIGN: Superiority, double-blind randomised controlled trial. SETTING: A total of 20 UK fetal medicine units. POPULATION: Pregnancies affected by FGR, defined as an abdominal circumference below the tenth centile with absent end-diastolic flow in the umbilical artery between 22+0 and 29+6 weeks of gestation. METHODS: Treatment with sildenafil (25 mg three times/day) or placebo until delivery or 32 weeks of gestation. MAIN OUTCOME MEASURES: All infants alive at hospital discharge were assessed for cardiovascular function and cognitive, speech/language and neuromotor impairment at 2 years of age. The primary outcome was survival without cerebral palsy or neurosensory impairment, or a Bayley-III composite score of >85. RESULTS: In total, 135 women were randomised between November 2014 and July 2016 (70 to sildenafil and 65 to placebo). We previously published that there was no improvement in time to delivery or perinatal outcomes with sildenafil. In all, 75 babies (55.5%) were discharged alive, with 61 infants eligible for follow-up (32 sildenafil and 29 placebo). One infant died (placebo), three mothers declined and ten mothers were uncontactable. There was no difference in neurodevelopment or blood pressure following treatment with sildenafil. Infants who received sildenafil had a larger head circumference at 2 years of age (median difference 49.2 cm, IQR 46.4-50.3, vs 47.2 cm, 95% CI 44.7-48.9 cm). CONCLUSIONS: Sildenafil therapy did not prolong pregnancy or improve perinatal outcomes and did not improve infant neurodevelopment in FGR survivors. Therefore, sildenafil should not be prescribed for this condition.

Randomized, Multicenter Study to Assess the Effects of Different Doses of Sildenafil on Mortality in Adults With Pulmonary Arterial Hypertension.

BACKGROUND: Sildenafil, approved for pulmonary arterial hypertension (PAH), has a recommended adult dose of 20 mg TID, with a previously approved 5-mg TID dose by the US Food and Drug Administration. Safety concerns arose because of common off-label use of higher doses, particularly after pediatric data linked higher doses to increased mortality. To assess this, the Food and Drug Administration mandated a study evaluating the effects of various sildenafil doses on mortality in adults with PAH. METHODS: This randomized, double-blind study compared sildenafil at doses of 5, 20, or 80 mg TID in adults with PAH. The primary objective was noninferiority of 80 mg of sildenafil versus 5 mg for all-cause mortality. Secondary end points included time to clinical worsening and change in 6-minute walk distance at 6 months. Interim analyses were planned at 50% and 75% of the anticipated mortality events. Safety and tolerability were assessed in the intention-to-treat population. RESULTS: The study was halted after the first interim analysis, demonstrating noninferiority for 80 mg of sildenafil versus 5 mg. Of 385 patients enrolled across all dose groups, 78 died. The primary analysis showed a hazard ratio of 0.51 (99.7% CI, 0.22-1.21; P<0.001 for noninferiority) for overall survival comparing 80 mg of sildenafil with 5 mg. Time to clinical worsening favored 80 mg of sildenafil compared with 5 mg (hazard ratio, 0.44 [99.7% CI, 0.22-0.89]; P<0.001). Sildenafil at 80 mg improved 6-minute walk distance from baseline at 6 months compared with 5 mg (least square mean change, 18.9 m [95% CI, 2.99-34.86]; P=0.0201). No significant differences were found between 80 mg of sildenafil and 20 mg in mortality, clinical worsening, and 6-minute walk distance. Adverse event-related drug discontinuations were numerically higher with 80 mg of sildenafil. CONCLUSIONS: Sildenafil at 80 mg was noninferior to sildenafil at 5 mg when examining all-cause mortality in adults with PAH. Secondary efficacy end points favored 80 mg of sildenafil over 5 mg. On the basis of these findings, the Food and Drug Administration recently revoked the approval of 5 mg of sildenafil for adults with PAH, reinforced 20 mg TID as the recommended dose, and now allows dose titration up to 80 mg TID, if needed. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02060487.

Combined on-demand sildenafil citrate and tramadol hydrochloride is an effective and safe treatment for premature ejaculation: A randomized placebo-controlled double-blind clinical trial.

Background: Premature ejaculation (PE) is a common sexual dysfunction that harms both sex partners. Aim: To evaluate the safety, efficacy and impact on sexual satisfaction scores of the combined use of tramadol HCl and sildenafil citrate for the treatment of PE. Methods: One hundred and sixty otherwise healthy males complaining of PE (primary/secondary) were enrolled in this randomized, double-blind, placebo-controlled study. Only 155 patients (age range 22-48 years) completed the study. Of them, 81 patients had primary PE, and 74 had secondary PE. The comparative groups included the placebo group (n = 34), sildenafil citrate 50 mg group (n = 39), tramadol HCl 100 mg group (n = 40), and the combination therapy group (n = 42). The treatment duration for all groups was 10 weeks. Outcomes: This combination is safe and effective. Results: Five patients discontinued the study, all from the placebo group, due to a lack of improvement over the treatment course. No significant differences were reported between groups before treatment as regards Intravaginal ejaculatory Latency Time (p = 0.8), satisfaction score (p = 0.7), age (p = 0.9), or duration of marriage (p = 0.9). There was a significant improvement in IELT after treatment with a placebo (p = 0.0001), associated with an insignificant improvement in satisfaction score (p = 1.0). In the other three groups, there was a significant improvement in IELT after treatment (p = 0.0001 for all), which coincided with a significant improvement in satisfaction scores in all three groups (p = 0.0001 for all). Clinical Implications: We recommend this combination in the treatment of premature ejaculation. Strengths: It is a prospective randomized double-blind placebo-controlled clinical trial. Limitations: Limited number of participants. Conclusion: Combined therapy of PE, whether primary or secondary, with sildenafil citrate 50 mg and tramadol HCl 100 mg is safe and effective; and its therapeutic effect is superior to the utilization of either agent alone.

Formulation and evaluation of inhaled Sildenafil-loaded PLGA microparticles for treatment of pulmonary arterial hypertension (PAH): A novel high drug loaded formulation and scalable process via hot melt extrusion technology (Part â ).

In recent years, several techniques were employed to develop a local sustained pulmonary delivery of sildenafil citrate (SC) as an alternative for the intravenous and oral treatment of pulmonary arterial hypertension (PAH). Most of these methods, however, need to be improved due to limitations of scalability, low yield production, low drug loading, and stability issues. In this study, we report the use of hot-melt extrusion (HME) as a scalable process for making Poly (lactic-co-glycolic acid) (PLGA) microparticles with high SC load. The prepared particles were tested in vitro for local drug delivery to the lungs by inhalation. Sodium bicarbonate was included as a porogen in the formulation to make the particles more brittle and to impart favorable aerodynamic properties. Six formulations were prepared with different formulation compositions. Laser diffraction analysis was used to estimate the geometric particle size distribution of the microparticles. In-vitro aerodynamic performance was evaluated by the next-generation cascade impactor (NGI). It was reported in terms of an emitted dose (ED), an emitted fraction (EF%), a respirable fraction (RF%), a fine particle fraction (FPF%), a mass median aerodynamic diameter (MMAD), and geometric standard deviation (GSD). The formulations have also been characterized for surface morphology, entrapment efficiency, drug load, and in-vitro drug release. The results demonstrated that PLGA microparticles have a mean geometric particle size between 6 and 14 µm, entrapment efficiency of 77 to 89 %, and SC load between 17 and 33 % w/w. Fifteen percent of entrapped sildenafil was released over 24 h from the PLGA microparticles, and seventy percent over 7 days. The aerodynamic properties included fine particle fraction ranging between 19 and 33 % and an average mass median aerodynamic diameter of 6-13 µm.

Efficient administration of a combination of nifedipine and sildenafil citrate versus only nifedipine on clinical outcomes in women with threatened preterm labor: a systematic review and meta-analysis.

BACKGROUND: Preterm labor (PTL) is a common and serious pregnancy disorder that can cause long-term neurological issues in the infant. There are conflicting studies concerning whether sildenafil citrate (SC) reduces preterm labor complications. Therefore, the meta-analysis aimed to examine the clinical outcomes in women with threatened PTL who received nifedipine plus SC therapy versus only nifedipine. METHODS: For the original articles, six databases were searched using relevant keywords without restriction on time or language until January 13, 2024. The Cochrane risk-of-bias tool for randomized trials (RoB) and the Risk of Bias Assessment Tool for Nonrandomized Studies (RoBANS) were both used to assess the risk of bias in randomized and non-randomized studies, and GRADE determined the quality of our evidence. Meta-analysis of all data was carried out using Review Manager (RevMan) version 5.1. RESULTS: Seven studies with mixed quality were included in the meta-analysis. The study found that combining nifedipine and SC resulted in more prolongation of pregnancy (MD = 6.99, 95% CI: 5.32, 8.65, p < 0.00001), a lower rate of delivery in the 1st to 3rd days after hospitalization (RR = 0.62, 95% CI: 0.50, 0.76, p < 0.00001), a higher birth weight (252.48 g vs. nifedipine alone, p = 0.02), and the risk ratio of admission to the neonatal intensive care unit (NICU) was significantly lower (RR = 0.62, 95% CI: 0.50, 0.76, p < 0.00001) compared to nifidepine alone. The evidence was high for prolongation of pregnancy, delivery rate 24-72 h after admission, and NICU admission, but low for newborn birth weight. CONCLUSIONS: Given the effectiveness of SC plus nifedipine in increased prolongation of pregnancy and birth weight, lower delivery in the 1st to 3rd days after hospitalization, and NICU admission, Gynecologists and obstetricians are suggested to consider this strategy for PTL management, although additional article rigor is required to improve the quality of the evidence.

3D human foreskin model for testing topical formulations of sildenafil citrate.

Sildenafil citrate is an approved drug used for the treatment of erectile dysfunction and premature ejaculation. Despite a widespread application, sildenafil citrate shows numerous adverse cardiovascular effects in high-risk patients. Local transdermal drug delivery of this drug is therefore being explored as an interesting and noninvasive alternative administration method that avoids adverse effects arised from peak plasma drug concentrations. Although human and animal skin represents the most reliable models to perform penetration studies, they involve a series of ethical issues and restrictions. For these reasons new in vitro approaches based on artificially reconstructed human skin or "human skin equivalents" are being developed as possible alternatives for transdermal testing. There is little information, however, on the efficiency of such new in vitro methods on cutaneous penetration of active ingredients. The objective of the current study was to investigate the sildenafil citrate loaded in three commercial transdermal vehicles using 3D full-thickness skin equivalent and compare the results with the permeability experiments using porcine skin. Our results demonstrated that, while the formulation plays an imperative role in an appropriate dermal uptake of sildenafil citrate, the D coefficient results obtained by using the 3D skin equivalent are comparable to those obtained by using the porcine skin when a simple drug suspension is applied (1.17 × 10-10 ± 0.92 × 10-10 cm2/s vs 3.5 × 102 ± 3.3 × 102 cm2/s), suggesting that in such case, this 3D skin model can be a valid alternative for ex-vivo skin absorption experiments.

The combined uterorelaxant effect of sildenafil and terbutalin in the rat: The potential benefit of co-administration of low doses.

Aims: Our aims were to investigate the uterus relaxant effect of sildenafil alone and co-administered with ß2-mimetic terbutaline in an isolated organ bath and to perform in vivo smooth muscle electromyographic studies in pregnant rats. The modifications in uterine cAMP/cGMP levels were also detected. Main methods: Contractions of non-pregnant and 5/15/18/20/22-day pregnant uterine rings were measured in an isolated organ bath system in the presence of sildenafil alone or with terbutaline. The uterine levels of cAMP and cGMP were determined by commercial ELISA assays. The in vivo efficacy of the combination was measured by smooth muscle electromyography. Key findings: Sildenafil reduced uterine contractions in vitro and in vivo; additionally, terbutaline significantly increased the uterorelaxant effect of sildenafil in the lower concentration or dose ranges. Terbutaline enhanced the cGMP level increasing effect of sildenafil. Significance: The co-administration of sildenafil and terbutaline could be a promising tocolytic combination to reduce maternal and foetal adverse events and increase efficacy.

What is the effect of sildenafil citrate intake on women undergoing assisted reproduction? A systematic review and meta-analysis of randomized controlled trials.

Assisted reproductive technologies (ART) have become a vital option for women facing fertility challenges. One of the potential interventions being explored is the use of sildenafil citrate (SC) to improve clinical outcomes in ART procedures. The aim of this study was to assess the impact of SC on clinical outcomes in women undergoing ART. A comprehensive literature search was conducted using multiple databases, including PubMed, Scopus, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials. The search covered studies from inception until April 15, 2023, and identified relevant randomized controlled trials (RCTs) for inclusion in the analysis. The endpoints were summarized as risk ratio (RR) or standardized mean difference (SMD) with 95% confidence interval (CI). After meticulous analysis, twenty-eight RCTs comprising 3,426 women were included in the study. The results revealed significant findings regarding the impact of SC on clinical pregnancy (CP) rates. Women receiving SC demonstrated a significantly higher probability of CP compared to the control group (n=21 RCTs, RR=1.43; 95% CI: 1.29, 1.59). Additionally, when SC was combined with other medications like clomiphene citrate (CC) or estradiol valerate, it further improved the likelihood of CP compared to these medications alone (RR=1.35, 95% CI: 1.19, 1.53; RR=1.55, 95% CI: 1.08, 2.22, respectively). Furthermore, the study observed that the mean endometrial thickness (ET) was significantly higher in women who received SC compared to the control group, which involved other active interventions or placebo (SMD=0.77, 95% CI: 0.20, 1.34). Particularly, the administration of SC resulted in a notably higher ET level compared to the placebo (SMD: 1.33, 95% CI: 0.15, 2.51). The findings suggest that luteal supplementation of SC can be considered a beneficial approach to enhance ET and improve the CP rate in women undergoing ART.

Polyelectrolyte-based solid dispersions for enhanced dissolution and pH-Independent controlled release of sildenafil citrate.

The aim of this study was to design a novel matrix tablet with enhanced dissolution and pH-independent controlled release of sildenafil citrate (SIL), a drug with pH-dependent solubility, by using solid dispersions (SDs) and polyelectrostatic interactions. SIL-loaded SDs were prepared using various polymeric carriers such as poloxamer 188, poloxamer 407, Soluplus®, polyvinylpyrrolidone (PVP) K 12, and PVP K 17 by the solvent evaporation method. Among these polymers, Soluplus® was found to be the most effective in SDs for enhancing the drug dissolution over 6 h in pH 6.8 intestinal fluid. SIL was well dispersed in Soluplus®-based SDs in an amorphous form. When the Soluplus®-based SDs were added in the tablet containing positively charged chitosan and negatively charged Eudragit® L100, the drug release rate was further modulated in a controlled manner. The charge density of the tablet was higher at pH 6.8 than at pH 1.2 due to the polyelectrostatic interaction between chitosan and Eudragit® L100. This interaction could provide a pH-independent controlled release of SIL. Our study demonstrates that a combinatory approach of Soluplus®-based SDs and polyelectrostatic interactions can improve the dissolution and pH-independent release performance of SIL. This approach could be a promising pharmaceutical strategy to design a matrix tablet of poorly water-soluble drugs for the enhanced bioavailability.

Predictors of the response to phosphodiesterase-5 inhibitors in pulmonary arterial hypertension: an analysis of the Spanish registry.

BACKGROUND: Achieving and maintaining a low-risk profile is associated with favorable outcome in pulmonary arterial hypertension (PAH). The effects of treatment on risk profile are variable among patients. OBJECTIVE: To Identify variables that might predict the response to treatment with phosphodiesterase-5 inhibitors (PDE-5i) in PAH. METHODS: We carried out a cohort analysis of the Spanish PAH registry in 830 patients diagnosed with PAH that started PDE5i treatment and had > 1 year follow-up. 644 patients started PDE-5i either in mono- or add-on therapy and 186 started combined treatment with PDE-5i and endothelin receptor antagonist (ERA). Responders were considered when at 1 year they: (1) were alive; (2) did not present clinical worsening; and (3) improved European Society of Cardiology/European Respiratory Society (ESC/ERS) risk score or remained in low-risk. Univariate and multivariate logistic regression models were used to analyze variables associated with a favorable response. RESULTS: Two hundred and ten patients (33%) starting PDE-5i alone were classified as responders, irrespective of whether it was mono- or add-on therapy. In addition to known predictors of PAH outcome (low-risk at baseline, younger age), male sex and diagnosis of portopulmonary hypertension (PoPH) or HIV-PAH were independent predictors of favorable response to PDE-5i. Diffusing capacity for carbon monoxide (DLco) ≤ 40% of predicted was associated with an unfavorable response. When PDE-5i were used in upfront combination, 58% of patients were responders. In this group, diagnosis of idiopathic PAH (IPAH) was an independent predictor of favorable response, whereas connective tissue disease-PAH was associated with an unfavorable response. CONCLUSION: Male sex and diagnosis of PoPH or HIV-PAH are predictors of favorable effect of PDE-5i on risk profile when used as mono- or add-on therapy. Patients with IPAH respond more favorably to PDE-5i when used in upfront combination. These results identify patient profiles that may respond favorably to PDE-5i in monotherapy and those who might benefit from alternative treatment strategies.

Phosphodiesterase-5 (PDE-5) Inhibitors as Therapy for Cerebrovascular Dysfunction in Chronic Traumatic Brain Injury.

Multiple phase III randomized controlled trials (RCTs) for pharmacologic interventions in traumatic brain injury (TBI) have failed despite promising results in experimental models. The heterogeneity of TBI, in terms of pathomechanisms and impacted brain structures, likely contributes to these failures. Biomarkers have been recommended to identify patients with relevant pathology (predictive biomarkers) and confirm target engagement and monitor therapy response (pharmacodynamic biomarkers). Our group focuses on traumatic cerebrovascular injury as an understudied endophenotype of TBI and is validating a predictive and pharmacodynamic imaging biomarker (cerebrovascular reactivity; CVR) in moderate-severe TBI. We aim to extend these studies to milder forms of TBI to determine the optimal dose of sildenafil for maximal improvement in CVR. We will conduct a phase II dose-finding study involving 160 chronic TBI patients (mostly mild) using three doses of sildenafil, a phosphodiesterase-5 (PDE-5) inhibitor. The study measures baseline CVR and evaluates the effect of escalating sildenafil doses on CVR improvement. A 4-week trial of thrice daily sildenafil will assess safety, tolerability, and clinical efficacy. This dual-site 4-year study, funded by the Department of Defense and registered in ClinicalTrials.gov (NCT05782244), plans to launch in June 2023. Biomarker-informed RCTs are essential for developing effective TBI interventions, relying on an understanding of underlying pathomechanisms. Traumatic microvascular injury (TMVI) is an attractive mechanism which can be targeted by vaso-active drugs such as PDE-5 inhibitors. CVR is a potential predictive and pharmacodynamic biomarker for targeted interventions aimed at TMVI. (Trial registration: NCT05782244, ClinicalTrials.gov ).

The effects of sildenafil citrate on intrauterine growth restriction: a systematic review and meta-analysis.

BACKGROUND: An increase in vascular resistance of uterine vessels is associated with intrauterine growth restriction (IUGR). Sildenafil citrate, a phosphodiesterase-5 inhibitor that stabilizes cyclic guanosine monophosphate (cGMP) and increases nitric oxide levels, improves placental perfusion by dilation of spiral arteries and is beneficial in managing IUGR. This study aims to determine the effectiveness of sildenafil citrate in improving perinatal outcomes in IUGR pregnancies. METHODS: Meta-analysis was performed on data extracted from all studies specific to sildenafil citrate in IUGR management, searching relevant articles on PubMed, Medline, Google Scholar, Embase, and Cochrane databases. Publications identified by the manual search, based on references in reviews, were also included. Dichotomous results were presented as risk ratio (95% confidence interval), while continuous results were expressed as mean difference (MD); samples represented by the random effects model. RESULTS: Nine trials were included where the sildenafil citrate effect was compared with a placebo or no intervention. A significant increase in birth weight [SMD (95% CI), 0.69 (0.31, 1.07)] was seen in IUGR pregnancies managed with sildenafil. However, gestational age (SMD (95% CI), 0.44 (-0.05, 0.94], fetal death rate [RR (95% CI), 0.56 (0.17, 1.79)] in IUGR pregnancies was not changed by sildenafil. Neonatal death [RR (95% CI), 0.93 (0.47, 1.86)] and neonatal intensive care unit (NICU) admissions [RR (95% CI), 0.76 (0.50, 1.17)] were not significantly different between sildenafil and control groups. CONCLUSION: Sildenafil citrate increases birth weight and prolonged pregnancies but did not affect stillbirth rate, neonatal death, and NICU admission. TRIAL REGISTRATION: The study was registered in PROSPERO on September 18, 2021 (CRD42021271992).

Effect of nifedipine with and without sildenafil citrate for the management of preterm labor in pregnant women: A randomized clinical trial.

Background: Preterm labor is one of the main causes of neonatal mortality and its treatment is still challenging. Objective: The study aimed to compare the effectiveness of nifedipine (Nif) with and without sildenafil citrate (SC) for the treatment of preterm labor in pregnant women. Materials and Methods: In this clinical trial study, 126 pregnant women referred to the Fatemieh hospital, Hamadan, Iran with a complaint of preterm labor were evaluated. Participants were randomly divided into 2 groups of Nif 20 mg orally (single dose), then 10 mg every 6-hr, and at the same time vaginal SC 25 mg every 8 hr (Nif + SC) or Nif alone. Treatment was continued for 48-72 hr if uterine contractions did not resolve in both groups. Delivery rates at the time of hospitalization and neonatal outcome were compared between the 2 groups. Results: No statistically significant difference was observed between the 2 study groups in terms of mean age, gestational age, body mass index, and parity. 76.2% of Nif + SC participants in the first 72 hr of hospitalization and 57.2% of Nif participants remained without delivery (p = 0.02). The neonatal hospitalization rate of the Nif + SC group in the neonatal intensive care unit was 25.4% and in the Nif group was 42.9% (p = 0.03). Conclusion: Nif with SC is superior to Nif alone in women at risk of preterm labor due to increasing gestational age and better neonatal outcomes.

Spider diagram and sustainability evaluation of UV-methods strategy for quantification of aspirin and sildenafil citrate in the presence of salicylic acid in their bulk and formulation.

The cutting-edge combination of aspirin (ASA) and sildenafil citrate (SIC) has been presented as a suggested dosage form for the treatment of thin endometrium and erectile dysfunction, particularly in patients with cardiovascular diseases. However, ASA is highly sensitive to degradation into its major deterioration product, known as salicylic acid (SA). Consequently, it is eminently essential to evolve approaches for the synchronous quantification of ASA and SIC in the presence of SA. The main objective of this work is to develop three approaches for the synchronous quantification of ASA and SIC in the presence of SA in their commixtures and suggested formulations without any prior separation. Three green UV-methods were employed for the synchronous quantification, namely: Dual Wavelength in Ratio Spectra (DW-RS), Advanced Amplitude Centering (AAC), and Double Divisor of Ratio Difference Derivative (DDRD-D1). In DW-RS and AAC two-wavelength manipulation was used for resolution, while in DDRD-D1 only an appropriate wavelength for the synchronous quantification of the triplex commixture was used. All approaches can be able to resolve the highly interfering spectrum of the three components presented in the triplex commixture. Good linearity was inspected in the range of 20.0-100.0, 5.0-50.0, and 4.0-60.0 µg/mL for the ASA, SIC, and SA, respectively. All developed approaches have been advocated in accordance with ICH guidelines. All results from these approaches are presented and statistically reconciled with the proclaimed HPLC method, with no considerable differences. Furthermore, the approaches' eco-friendliness was predestined by Analytical Greenness (AGREE), and the complex GAPI. Moreover, the sustainability of the used solvent was evaluated by Green Solvents Selecting Tool (GSST); in addition, the greenness of the solvent was evaluated by Greenness Index tool with a spider diagram. The suggested UV-methods may be employed for routine quality control studies of the suggested formulations ASA & SIC since they were considered sustainable, economical, and effective.

Comparative Evaluation of Sildenafil Citrate and Estrogen as an Adjuvant Therapy for Treatment of Unexplained Infertility in Women.

BACKGROUND: Uterine blood flow determines endometrial thickness. This study examined how vaginal sildenafil citrate and estradiol valerate altered endometrial thickness, blood flow, and fertility in infertile women. METHODS: This study observed 148 infertile women whose infertility was unexplained. Group 1 comprised 48 patients who received oral estradiol valerate (Cyclo-Progynova 2 mg/12 h white tablets) from day 6 till ovulation was initiated with clomiphene citrate. A number of 50 participants in group 2 received oral sildenafil (Respatio 20 mg/12 h film-coated tablets) for 5 days starting the day after their previous menstrual period and finishing on the day they ovulated with clomiphene citrate. Group 3 was the control group, with 50 patients receiving clomiphene citrate (Technovula 50 mg/12 h tablets) ovulation induction from the 2nd to 7th day of cycle. All patients had transvaginal ultrasounds to determine ovulation, follicle count, and fertility. Miscarriage, ectopic pregnancy, and multiple pregnancies were monitored for three months. RESULTS: The three groups' mean ETs differed statistically at p = 0.0004. A statistically significant difference was found between the three groups in terms of the number of follicles, with 69% of patients in group 1 having one and 31% having two or more, 76% of patients in group 2 having one and 24% having two or more, and 90% of patients in the control group having one and 10% having two or more (p = 0.038). The clinical pregnancy rates of the three groups were 58%, 46%, and 27%, respectively (p = 0.005). The distribution of all side effects was not statistically different between the three groups. CONCLUSION: It is possible to claim that adding oral estrogen to clomiphene citrate therapy as an adjuvant therapy can improve endometrial thickness and, as a result, increase the pregnancy rates in unexplained infertility compared to sildenafil, especially in cases where the infertility has lasted less than two years. Most people who take sildenafil end up with a mild headache.

Sildenafil citrate ameliorates the adverse effects of cryopreservation on sperm quality in asthenozoospermic men.

In this study, the effects of Sildenafil Citrate on the sperm quality during cryopreservation in the asthenozoospermic patients were investigated for the first time. Thirty semen samples were collected from asthenozoospermic patients and each sample was divided into 3 groups: Control (fresh), Freeze and Freeze + Sildenafil. In each groups the sperm parameters, DNA fragmentation, acrosome integrity, protamine deficiency, mitochondrial membrane potential, plasma membrane integrity, the expression of Bcl-2 and HSP70 genes, as well as the level of Tumor necrosis factor-alpha, Malondialdehyde and antioxidants (Catalase, Glutathione, and Superoxide dismutase) in sperm were assessed. Data were analyzed statistically using Repeated Measure Analysis. The level of Malondialdehyde and Tumor necrosis factor-alpha, morphological abnormalities, DNA fragmentation, protamine deficiency and the expression of Bcl-2 and HSP70 genes increased significantly in the Freeze group compared to the Control, while the level of sperm parameters and antioxidants, plasma membrane integrity, mitochondrial membrane potential and acrosomal integrity significantly decreased. In the Freeze + Sildenafil group, compared to the Freeze group, all the mentioned parameters were significantly reversed except for the acrosomal integrity (decreased even more) and the expression of Bcl-2 (increased even more) and HSP70 genes (with no change). Although adding Sildenafil to the freezing medium decreased the adverse effects of freezing on the sperm of asthenozoospermic patients and improved sperm quality, but it also caused premature acrosome reaction. Therefore, we suggest the consumption of Sildenafil along with another antioxidant, to benefit from the favorable effects of Sildenafil as well as to maintain the integrity of the sperm acrosome.

Antioxidant-rich Terminalia catappa fruit exerts antihypertensive effect via modulation of angiotensin-1-converting enzyme activity and H2S/NO/cGMP signalling pathway in Wistar rats.

INTRODUCTION: The present study aimed at investigating the effect of Terminalia catappa fruits on blood pressure, NO/cGMP signalling pathway, angiotensin-1-converting enzyme and arginase activity, and oxidative stress biomarkers in L-NAME-induced hypertensive rats. MATERIALS AND METHODS: Forty-two Wistar rats were divided into seven groups. Hypertension was induced via oral administration of 40 mg/kg of L-NAME for 21 days. Thereafter, the hypertensive rats were treated with Terminalia catappa fruit-supplemented diet and sildenafil citrate for 21 days. The blood pressure was measured and cardiac homogenate was prepared for biochemical analyses. RESULTS: The results showed that L-NAME caused a significant (p < 0.05) increase in systolic and diastolic blood pressure, and heart rate as well as ACE, arginase and PDE-5 activity, with a simultaneous decrease in NO and H2S levels as well as increased oxidative stress biomarkers. However, treatment with Terminalia catappa fruits-supplemented diets and sildenafil citrate lowered blood pressure and modulated ACE, arginase, and PDE-5 activity, improved NO and H2S levels, as well as antioxidant status. CONCLUSION: Findings presented in this study provide useful information on the antihypertensive property of Terminalia catappa fruits, alongside some possible mechanisms. Hence, Terminalia catappa fruits could be considered a dietary regimen and functional food in alleviating hypertension.

Development and Optimization of Sildenafil Orodispersible Mini-Tablets (ODMTs) for Treatment of Pediatric Pulmonary Hypertension Using Response Surface Methodology.

The availability of age-appropriate oral dosage forms for pediatric patients has remained a challenge. Orodispersible mini-tablets (ODMTs) are a promising delivery system for pediatric patients. The purpose of this work was the development and optimization of sildenafil ODMTs as a new dosage form for the treatment of pulmonary hypertension in children using a design-of-experiment (DoE) approach. A two-factor, three levels (32) full-factorial design was employed to obtain the optimized formulation. The levels of microcrystalline cellulose (MCC; 10-40% w/w) and partially pre-gelatinized starch (PPGS; 2-10% w/w) were set as independent formulation variables. In addition, mechanical strength, disintegration time (DT), and percent drug release were set as critical quality attributes (CQAs) of sildenafil ODMTs. Further, formulation variables were optimized using the desirability function. ANOVA analysis proved that MCC and PPGS had a significant (p < 0.05) impact on CQAs of sildenafil ODMTs with a pronounced influence of PPGS. The optimized formulation was achieved at low (10% w/w) and high (10% w/w) levels of MCC and PPGS, respectively. The optimized sildenafil ODMTs showed crushing strength of 4.72 ± 0.34 KP, friability of 0.71 ± 0.04%, DT of 39.11 ± 1.03 s, and sildenafil release of 86.21 ± 2.41% after 30 min that achieves the USP acceptance criteria for ODMTs. Validation experiments have shown that the acceptable prediction error (<5%) indicated the robustness of the generated design. In conclusion, sildenafil ODMTs have been developed as a suitable oral formulation for the treatment of pediatric pulmonary hypertension using the fluid bed granulation process and the DoE approach.

Solid state 13C NMR spectroscopy as a tool for identification of counterfeit Viagra tablets and guide for develop new identification approach of falsified product.

Counterfeit drugs are a global problem that is directly related to the safety and effectiveness of pharmacotherapy. The black market for counterfeit products is constantly growing and related to the wide availability through online shopping. Therefore, there is a constant need to develop analytical methods that would allow for the unambiguous identification of counterfeit products from the original ones. One of such techniques is solid-state NMR spectroscopy, which allows for direct registration and analysis of spectra of multicomponent solid forms of pharmaceutical formulations. The paper explores the possibility of using this technique in the identification of counterfeit Viagra tablets. In this study, solid-state NMR has been used to detect the non-pharmacopoeial cellulose present in the samples of counterfeit Viagra tablets. Besides, the NMR results allowed to develop a rapid dying technique that can be used to distinguish between the counterfeit and original drug. It has been shown that solid-state NMR spectroscopy allows for numerous analyses such as identification of counterfeit products, assessment of the composition of analyte, estimation of qualitative differences between the original and falsified product, and the development of simple analytical methods based on tablets composition differences.