Search Results (12)

Have you ever looked at a powder diffractogram during a routine qualitative test and wondered how much of a particular powder compound is in the powder material? Several methods can work this out, but none of them could be used in our case because something was missing from each in performing a rapid quantity test for an active ingredient in a tablet. A semiquantitative method of an X-ray powder diffraction analysis of products containing sildenafil citrate is proposed. This method utilizes calibration curves for the most common compositions encountered in falsified and not-registered Viagra analogues. Sildenafil doses are established for singularly prepared powder probes of a medicinal product, and two runs of data collection are used: the first, the fast one, for the qualitative analysis of the product, and the second for selected 2θ regions for the API and identified excipients. An example of a product composed mainly of sildenafil citrate, gypsum and microcrystalline cellulose is discussed in detail. The data obtained from X-ray experiments were compared with the results obtained from validated liquid chromatography coupled to a diode array detector and mass spectrometry methods. Full article

New ruthenium olefin metathesis catalysts containing N-heterocyclic carbene (NHC) connected by a linker tether to a benzylidene ligand were studied. Such obtained self-chelated Hoveyda–Grubbs type complexes existed in the form of an organometallic polymer but could still catalyze olefin metathesis after being dissolved in an organic solvent. Although these polymeric catalysts exhibited a slightly lower activity compared to structurally related nonpolymeric catalysts, they were successfully used in a number of ring-closing metathesis reactions leading to a variety of heterocyclic compounds, including biologically and pharmacologically related analogues of cathepsin K inhibitor and sildenafil (Viagra™). In the last case, a good solubility of a polymeric catalyst in toluene allowed the separation of the product from the catalyst via simple filtration. Full article

Sildenafil citrate (SLC) is a frequently used medication (Viagra®) for the treatment of erectile dysfunction (ED). Due to its poor solubility, SLC suffers from a delayed onset of action and poor bioavailability. Hence, the aim of the proposed work was to prepare and evaluate solid dispersions (SDs) with hydrophilic polymers (Kolliphor® P188, Kollidon® 30, and Kollidon®-VA64), in order to enhance the dissolution and efficacy of SLC. The SLC-SDs were prepared using a solvent evaporation method (at the ratio drug/polymer, 1:1, w/w) and characterized by Differential Scanning Calorimetry (DSC), Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), Scanning electron microscope (SEM), drug content, yield, and in vitro release studies. Based on this evaluation, SDs (SLC-KVA64) were optimized, with a maximum release of drug (99.74%) after 2 h for all the developed formulas. The SDs (SLC-KVA64) were further tested for sexual behavior activity in male rats, and significant enhancements in copulatory efficiency (81.6%) and inter-copulatory efficiency (44.9%) were noted in comparison to the pure SLC drug, when exposed to the optimized SLC-KVA64 formulae. Therefore, SD using Kollidon®-VA64 could be regarded as a potential strategy for improving the solubility, in vitro dissolution, and therapeutic efficacy of SLC. Full article

In hypertensive individuals, platelet morphology and function have been discovered to be altered, and this has been linked to the development of vascular disease, including erectile dysfunction (ED). The impact of nutritional supplementation with Cyperus esculentus (tiger nut, TN) and Tetracarpidium conophorum (walnut, WN) on androgen levels, ectonucleotidases, and adenosine deaminase (ADA) activities in platelets from L-NAME (Nω-nitro-L-arginine methyl ester hydrochloride) challenged rats were investigated. We hypothesized that these nuts may show a protective effect on platelets aggregation and possibly enhance the sex hormones, thereby reverting vasoconstriction. Wistar rats (male; 250–300 g; n = 10) were grouped into seven groups as follows: basal diet control group (I); basal diet/L-NAME/Viagra (5 mg/kg/day) as positive control group (II); ED-induced group (basal diet/L-NAME) (III); diet supplemented processed TN (20%)/L-NAME (IV); diet supplemented raw TN (20%)/L-NAME (V); diet supplemented processed WN (20%)/L-NAME (VI); and diet supplemented raw WN (20%)/L-NAME (VII). The rats were given their regular diet for 2 weeks prior to actually receiving L-NAME (40 mg/kg/day) for ten days to induce hypertension. Platelet androgen levels, ectonucleotidases, and ADA were all measured. L-NAME considerably lowers testosterone levels (54.5 ± 2.2; p < 0.05). Supplementing the TN and WN diets revealed improved testosterone levels as compared to the control (306.7 ± 5.7), but luteinizing hormone levels remained unchanged. Compared to control groups, the L-NAME-treated group showed a rise in ATP (127.5%) hydrolysis and ADA (116.7%) activity, and also a decrease in ADP (76%) and AMP (45%) hydrolysis. Both TN and WN supplemented diets resulted in substantial (p < 0.05) reversal effects. Enhanced testosterone levels and modulation of the purinergic system in platelets by TN and WN could be one of the mechanisms by which they aid in vasoconstriction control. Full article

Piperazine ranks as the third most common nitrogen heterocycle in drug discovery, and it is the key component of several blockbuster drugs, such as Imatinib (also marketed as Gleevec) or Sildenafil, sold as Viagra. Despite its wide use in medicinal chemistry, the structural diversity of piperazines is limited, with about 80% of piperazine-containing drugs containing substituents only at the nitrogen positions. Recently, major advances have been made in the C–H functionalization of the carbon atoms of the piperazine ring. Herein, we present an overview of the recent synthetic methods to afford functionalized piperazines with a focus on C–H functionalization. Full article

Sildenafil citrate undergoes first-pass metabolism, resulting in poor oral bioavailability at 25–41% of the administered dose. This study aimed to design and optimize fast-disintegrating tablets for the sublingual delivery of sildenafil citrate to improve bioavailability and facilitate rapid onset of action. The design-of-experiment (DoE) approach using 3² full factorial design was conducted to develop a new formulation of sildenafil fast-disintegrating sublingual tablets (FDSTs) using the fluid-bed granulation technique. The levels of partially pre-gelatinized starch (5–15%) and microcrystalline cellulose (10–60%) were selected as independent formulation variables. The prepared FDSTs were investigated for physical properties. Further, the optimum formulation was chosen for in vivo study in rabbits. Regression analysis showed that independent variables have a significant (p < 0.05) influence on critical attributes of FDSTs. The optimized formulation showed acceptable mechanical strength (friability < 1.0%) with very fast disintegration (14.561 ± 0.84 s) and dissolution (94.734 ± 2.76% after 15 min). Further, the optimized formulation demonstrated a significant increase (p < 0.01) in C_max and AUC₀–∞ with short t_max compared to the market product (Viagra^®). Based on these results, using the DoE approach, a high level of assurance was achieved for FDSTs’ product quality and performance. Full article

Sildenafil is the active substance in Viagra^® tablets, which is approved by the FDA to treat sexual dysfunction in men. Poor solubility and short half-life, however, can limit the span of its effectiveness. Therefore, this study focused on an oral controlled release matrix system with the aim to improve solubility, control the drug release, and sustain the duration of drug activity. The controlled release matrices were prepared with poloxamer-188, hydroxypropyl methylcellulose, and magnesium stearate. Various formulations of different ratios were developed, evaluated in vitro, and assessed in silico. Poloxamer-188 appeared to have a remarkable influence on the release profile of sildenafil citrate. In general, the rate of drug release decreased as the amount of polymer was gradually increased in the matrix system, achieving a maximum release period over 12 h. The in silico assessment by using the GastroPlus™ PBPK modeling software predicted a significant variation in C_max, t_max, t_1/2, and AUC_0-t among the formulations. In conclusion, the combination of polymers in matrix systems can have substantial impact on controlling and modifying the drug release pattern. Full article

Phosphodiesterase type 5 (PDE5) inhibitors such as Viagra^® (sildenafil citrate) have demonstrated efficacy in the treatment of erectile dysfunction (ED) by inducing cyclic guanosine monophosphate (cGMP) elevation followed by vasodilation and increased blood flow. It also exerts minor inhibitory action against PDE6, which is present exclusively in rod and cone photoreceptors. The effects of sildenafil on the visual system have been investigated in a wide variety of clinical and preclinical studies due to the fact that a high dose of sildenafil may cause mild and transient visual symptoms in some patients. A literature review was performed using PubMed, Cochrane Library and Clinical Trials databases from 1990 up to 2020, focusing on the pathophysiology of visual disorders induced by sildenafil. The aim of this review was not only to gather and summarize the information available on sildenafil clinical trials (CTs), but also to spot subpopulations with increased risk of developing undesirable visual side effects. This PDE inhibitor has been associated with transient and reversible ocular side effects, including changes in color vision and light perception, blurred vision, photophobia, conjunctival hyperemia and keratitis, and alterations in the electroretinogram (ERG). Sildenafil may induce a reversible increase in intraocular pressure (IOP) and a few case reports suggest it is involved in the development of nonarteritic ischemic optic neuropathy (NAION). Reversible idiopathic serous macular detachment, central serous retinopathy and ERG disturbances have been related to the significant impact of sildenafil on retinal perfusion. So far, sildenafil does not seem to cause permanent toxic effects on chorioretinal tissue and photoreceptors as long as the therapeutic dose is not exceeded and is taken under a physician’s direction to treat a medical condition. However, the recreational use of sildenafil can lead to harmful side effects, including vision changes. Full article

Substandard and falsified medicines are often reported worldwide. An accurate and rapid detection method for falsified medicines is needed to prevent human health hazards. Raman scattering spectroscopy has emerged as a non-destructive analysis method for the detection of falsified medicines. In this laboratory study, Raman spectroscopy was performed to evaluate the applicability of the ultra-compact Raman scattering spectrometer (C13560). Principal component analysis (PCA) was also performed on the Raman spectra. This study analyzed tadalafil (Cialis), vardenafil (Levitra), and sildenafil (Viagra) tablets. We tested the standard product and products purchased from the internet (genuine or falsified). For Cialis and Levitra, all falsified tablets were identified by the Raman spectra and PCA score plot. For Viagra, the Raman spectra of some falsified tablets were almost comparable to the standard tablet. The PCA score plots of falsified tablets were dispersed, and some plots of falsified tablets were close to the standard tablet. In conclusion, C13560 was useful for the discrimination of falsified Cialis and Levitra tablets, whereas some falsified Viagra tablets had Raman spectra similar to that of the standard tablet. The development of detection methods that can be introduced in various settings may help prevent the spread of falsified products. Full article

Medicine falsification is a global issue. Viagra, an erectile dysfunction therapeutic (EDT) medicine consisting primarily of sildenafil citrate, is the most commonly falsified medicine worldwide. Recently falsified EDTs have been reported multiple times in developing countries. The globalization of falsified EDTs has become a concern. In the present study, we selected sildenafil citrate tablets as an indicator and examined samples from a developing country, Cambodia, to investigate the availability of falsified sildenafil tablets in Cambodia and verify the current globalization status of falsified medicines from the standpoint of a developing country. Six samples of the originator Viagra, and 68 samples of generic sildenafil products were purchased from private drug outlets and wholesalers in Phnom Penh, Svay Rieng, and Battambang. The samples’ manufacturers were contacted to authenticate the samples. The quantities and dissolution rates of active ingredients were measured by a high-performance liquid chromatography system with photodiode array. Five generic samples were strongly suspected to be falsified medicines because of their extremely low quality; however, there was little distribution and no falsified medicine alleged to be produced by the originator of Viagra, which charges high prices. That finding indicates that falsification reflects local economic circumstances. Full article

Sildenafil, a phosphodiesterase-5 inhibitor sold as Viagra, is a cardioprotector against myocardial ischemia/reperfusion (I/R) injury. Our study explored whether sildenafil protects against I/R-induced damage in a porcine cardiac arrest and resuscitation (CAR) model via modulating the renin-angiotensin system. Male pigs were randomly divided to three groups: Sham group, Saline group, and sildenafil (0.5 mg/kg) group. Thirty min after drug infusion, ventricular fibrillation (8 min) and cardiopulmonary resuscitation (up to 30 min) was conducted in these animals. We found that sildenafil ameliorated the reduced cardiac function and improved the 24-h survival rate in this model. Sildenafil partly attenuated the increases of plasma angiotensin II (Ang II) and Ang (1–7) levels after CAR. Sildenafil also decreased apoptosis and Ang II expression in myocardium. The increases of expression of angiotensin-converting-enzyme (ACE), ACE2, Ang II type 1 receptor (AT1R), and the Ang (1–7) receptor Mas in myocardial tissue were enhanced after CAR. Sildenafil suppressed AT1R up-regulation, but had no effect on ACE, ACE2, and Mas expression. Sildenafilfurther boosted the upregulation of endothelial nitric oxide synthase (eNOS), cyclic guanosine monophosphate (cGMP) and inducible nitric oxide synthase(iNOS). Collectively, our results suggest that cardioprotection of sildenafil in CAR model is accompanied by an inhibition of Ang II-AT1R axis activation. Full article

Dystrophin-glycoprotein complex (DGC) is an important structural unit in skeletal muscle that connects the cytoskeleton (f-actin) of a muscle fiber to the extracellular matrix (ECM). Several muscular dystrophies, such as Duchenne muscular dystrophy, Becker muscular dystrophy, congenital muscular dystrophies (dystroglycanopathies), and limb-girdle muscular dystrophies (sarcoglycanopathies), are caused by mutations in the different DGC components. Although many early studies indicated DGC plays a crucial mechanical role in maintaining the structural integrity of skeletal muscle, recent studies identified novel roles of DGC. Beyond a mechanical role, these DGC members play important signaling roles and act as a scaffold for various signaling pathways. For example, neuronal nitric oxide synthase (nNOS), which is localized at the muscle membrane by DGC members (dystrophin and syntrophins), plays an important role in the regulation of the blood flow during exercise. DGC also plays important roles at the neuromuscular junction (NMJ) and in the brain. In this review, we will focus on recently identified roles of DGC particularly in exercise and the brain. Full article