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Hesperidin is a polyphenol derived from citrus fruits that has a broad potential for biological activity and the ability to positively modify the intestinal microbiome. However, its activity is limited by its low solubility and, thus, its bioavailability—this research aimed to develop a zein-based hesperidin system with increased solubility and a sustained release profile. The study used triple systems enriched with solubilizers to maximize solubility. The best system was the triple system hesperidin-zein-Hpβ-CD, for which the solubility improved by more than six times. A significant improvement in the antioxidant activity and the ability to inhibit α-glucosidase was also demonstrated, due to an improved solubility. A release profile analysis was performed in the subsequent part of the experiments, confirming the sustained release profile of hesperidin, while improving the solubility. Moreover, the ability of selected probiotic bacteria to metabolize hesperidin and the effect of this flavonoid compound on their growth were investigated.

Na trgu je vedno več zdravilnih učinkovin, ki so težko vodotopne in imajo posledično slabšo absorpcijo in biološko uporabnost. Eden izmed največjih izzivov farmacevtske industrije je povečanje biološke uporabnosti takšnih učinkovin. Izdelava trdnih disperzij z iztiskanjem talin kot napredna in kontinuirana tehnologija tako postaja vedno bolj aktualna strategija za povečanje hitrosti raztapljanja učinkovine. Namen magistrske naloge je bil literaturni pregled in analiza znanstvenih člankov na temo izdelave trdnih disperzij z iztiskanjem talin, katerih namen je bil povečati hitrost raztapljanja težko vodotopnih učinkovin. S pomočjo dveh podatkovnih baz smo pridobili 53 člankov, ki so ustrezali našim kriterijem. Po pregledu člankov smo ugotovili, da so raziskovalci večinoma uporabili učinkovine iz terapevtske skupine za bolezni srca in ožilja (32 %), ki predstavljajo eno najpogosteje predpisanih skupin zdravil, ki se največkrat uporabljajo v vsakdanjem življenju. Za izdelavo trdnih disperzij so uporabili različne nosilce. Najpogosteje uporabljeni so bili hidrofilni polimeri, kot sta KollidonVA64 ter Soluplus, ki se pojavita v 26 % in 22 % formulacijah. Opazili pa smo tudi uporabo polimerov, ki se običajno uporabljajo za druge namene, kot so npr. gastrorezistentni polimeri ali surfaktanti. Zanimalo nas je tudi, kako uspešni so bili raziskovalci pri izboljšanju hitrosti raztapljanja trdnih disperzij v primerjavi s čisto učinkovino. Zelo malo raziskav pa je nastalo trdno disperzijo nadalje obdelalo v končno farmacevtsko obliko, saj so se raziskovalci za izdelavo končne farmacevtske oblike odločili le pri 36 % formulacijah. Kljub večanju števila člankov pa nismo našli članka, ki bi spremljal vse vidike, ki so pomembni pri razvoju trdnih disperzij z iztiskanjem talin (formulacija trdnih disperzij, procesni pogoji za izdelavo, nadaljnja obdelava, končna farmacevtska oblika). The number of drug substances with poor aqueous solubility and consequently poor absorption and bioavailability is increasing on the market. One of the biggest challenges for the pharmaceutical industry is increasing the bioavailability of such drug substances. The production of solid dispersions by hot-melt extrusion as an advanced and continuous technique is becoming an increasingly relevant strategy for the enhancement of solubility of poorly soluble drugs. The purpose of this Master's Thesis was to prepare a literature review and analysis of scientific articles which involve preparation of solid dispersions by hot-melt extrusion with aim of enhancing the solubility of poorly water-soluble drug substances. With the use of two databases, we obtained 53 articles that met our criteria. After reviewing them we found out that researchers mostly used drugs from the therapeutic group of cardiovascular diseases (32 %), which are one of the most commonly prescribed drugs. Various carries have been used to produce solid dispersions. Hydrophilic polymers such as KollidonVA64 (26 %) and Soluplus (22 %) were most commonly used. We also observed the use of polymers of polymers (gastroresistant polymers and surfactants) that are commonly used for other purposes. We were also interested in how successful the researchers were in improving the dissolution of solid dispersion compared to pure drug. Only a few research articles included downstream processing of the obtained solid dispersions into final dosage form. Only 36% of researchers decided to make the final dosage form. Despite the increase in the number of articles, we did not find the article that would cover all aspects that are important in the development of solid dispersion by hot-melt extrusion (solid dispersion formulation, process conditions for production, downstreaming, final dosage form).

The poor solubility and low stability of rifampicin limited its therapeutic efficacy. One of the common strategies is to form an inclusion complex to address the problems. In this study, acyclic cucurbit[n]uril was used for encapsulation of rifampicin to form an inclusion complex. The inclusion complex was prepared by the kneading method and characterized by DSC, SEM, FT-IR, NMR, PXRD, and UV-Vis spectroscopy. The results confirmed the formation of 1:1 inclusion complex. The drug content was calculated to be 27.35 ± 0.54%. The aqueous solubility of rifampicin was increased 20-fold by complexation with acyclic cucurbit[n]uril. Moreover, the thermo-stability and photo-stability of free rifampicin and inclusion complex were investigated by HPLC. Rifampicin was stabilized by encapsulating the piperazine ring in the cavity of acyclic cucurbit[n]uril. In addition, the MIC of free RIF and RIF‧ACB were determined by using in vitro experiments. It was found that rifampicin complexed by acyclic cucurbit[n]uril exhibited similar antibacterial activities against strain H37Rv to rifampicin alone.

Polyimides (PIs) possess excellent thermal and mechanical properties, but their poor solubility in organic solvents restricts their utility. Numerous studies have focused on improving PI solubility by weakening inter-molecular interactions within the polymer. The polyimide composed of aromatic anhydride, 6,6′-(hexafluoroisopropylidene)dipthalic anhydride and aromatic diamine, 4,4′-oxidianiline, is known to be soluble, but solubility at room temperature is very limited. In this study, a soluble polyimide copolymer, 2,2-bis(3-amino-4-hydroxyphenyl)hexafluoropropane (Bis-ap-af), a diamine containing hydroxyl groups, was incorporated into the above-mentioned PI via chemical and thermal imidization. Chemical imidization resulted in the acetylation of the hydroxyl groups of Bis-ap-af units, while the hydroxyls remained intact under thermal imidization conditions. The acetoxy-containing soluble polyimide copolymers displayed improved solubility in a number of organic solvents compared to the conventional PI, and the copolymer films maintained their mechanical properties and presented reduced yellowness.

A two‐step synthesis for methionine‐containing hydrophobic and/or aggregation‐prone peptides is presented that takes advantage of the reversibility of methionine oxidation. The use of polar methionine sulfoxide as a building block in solid‐phase peptide synthesis improves the synthesis quality and yields the crude peptide, with significantly improved solubility compared to the reduced species. This facilitates the otherwise often laborious peptide purification by high‐performance liquid chromatography. The subsequent reduction proceeds quantitatively. This approach has been optimised with the methionine‐rich Tar‐DNA‐binding protein 43 (307–347), but is also more generally applicable, as demonstrated by the syntheses of human calcitonin and two aggregation‐prone peptides from the human prion protein., Ox and red: A synthesis and purification method for methionine‐containing hydrophobic and aggregation‐prone peptides that exploits the reversibility of methionine oxidation is reported. Incorporating methionine sulfoxide rather than methionine reduces aggregation during peptide synthesis and significantly facilitates peptide purification due to the increased peptide polarity. Final reduction to methionine proceeds smoothly and quantitatively.

In the present research, newly developed complex with sodium caprylate was investigated for solubility and dissolution enhancement of eluxadoline. Complexes were prepared in different ratios by solvent evaporation method and characterised solubility study, Infrared spectroscopy (IR), Diffrential scanning calorimetry (DSC), X-Ray Diffraction (XRD), drug content analysis and in vitro Drug release. The solubility and dissolution rate revealed most suitable ratio of eluxadoline and sodium caprylate (1:4). The IR, DSC and X-RD data also confirmed the results. It was concluded that complex prepared with (1:4 drug:sodium caprylate ratio) using solvent evaporation method showed significant improvement in solubility and drug dissolution.

The purpose of this study was to improve the processability of rice powder using fluidised-bed granulation technology. Bukkyungmi-rice granules were prepared by fluidised-bed granulation for 1 and 2 h using water, 5% lactose (w/v) and 5% dextrin (w/v) solutions as dispersants. The particle size of Bukkyungmi-rice granules increased from 574.83 to 728.07 μm. Granules were produced due to pore formation, and the produced particles could be dispersed easily without any entanglement. The water solubility of the produced rice granules is 1.91–6.74%, which reflects the improvement in their quality with increased treatment time. In particular, Bukkyungmi-rice granules processed in 5% dextrin showed excellent settleability. The enthalpy (ΔH) was found to be the highest for Bukkyungmi-rice granules processed in 5% dextrin for 2 h by differential scanning calorimetry. The results indicated that rice granules obtained by fluidised-bed granulation could be used in various types of rice-based foods.

Porous silica-based drug delivery systems have shown substantial potential for improving the oral delivery of poorly water-soluble drugs.The major problem with nateglinide, a BCS Class II drug, is pHdependent solubility, limited aqueous solubility, poor dissolution and variable bioavailability. The aim of the present investigation was to develop a lipid-based solid formulation of nateglinide, as a strategy to improve both the solubility and the dissolution rate of the drug in a tablet dosage form. The silica lipid hybrid (SlH) particles were formulated using Miglyol812 and Acrysol el 135 as liquid lipid vehicles as well aslabrasol and Transcutol HP as surfactants.Nateglinide was dissolved in different lipids and later adsorbed on highly porous silica Sylloid PF244 to obtain free-flowing powders. The prepared nateglinide SlH was characterized by FT-IR, DSC, and XRD.Nateglinide SlH was evaluated for solubility and dissolution. SlH of NTG prepared with Miglyol 812 and Transcutol HP enhanced solubility of NTG 57.21 fold. From the study, it may be concluded that the oral solid lipid-based formulation, SlH has an improved potential for enhancing solubility and dissolution of BCS class II drugs like nateglinide.

Less local availability and higher skin permeation restrict wide application of silver sulfadiazine (SSD) formulations against infectious burn wound. We aimed to develop β-cyclodextrin inclusion complex-based in situ pluronic gel of SSD (β-CD-ssd P-Gel). Formation of inclusion complex was confirmed by FT-IR, DSC, SEM, and XRD and checked for improved solubility. Poloxamer (407/118)-based in situ gel of inclusion complex was prepared and characterized for its gelation temperature (33.50 °C), viscosity (1159.25 ± 5.60 cps), pH (6.4 ± 0.56), and drug content (91.56 ± 1.62%). The developed gel showed slow drug release and slow permeation of the drug through the skin. It showed broader zone of Staphylococcus aureus growth inhibition (31 ± 0.20 mm) and high wound contraction (98.89%) when compared with the marketed formulation (26 ± 0.20 mm and 58.00%, respectively). A consistent, biocompatible, β-CD-ssd P-Gel was prepared successfully. It was found able to ensure increased local availability by forming viscous gel below body temperature, high SSD availability at the desired site, and high efficacy against infectious wound.

Objective: Nateglinide is a commonly used oral hypoglycemic, biopharmaceutical classification system Class II drug, which shows relatively poor water solubility and variable bioavailability. The objective of the present investigation was to develop the binary and ternary solid dispersions of nateglinide for improved solubility and dissolution. Methods: Nateglinide solid dispersions were prepared by a common solvent evaporation method. Polymers like soluplus, kolliphor P188, sylloid 244FP, gelucire 48/16, affinisol (HPMCAS), HPβCD, βCD were used in different combinations. The physicochemical characterization of the optimized ternary dispersion was studied by using FT-IR, DSC, and PXRD. Solubility and dissolution behavior of all dispersions were studied. Result: From all prepared ternary solid dispersions, nateglinide dissolution was significantly faster than pure nateglinide. With ternary solid dispersion of NTG, soluplus and kolliphor P188 there was a big improvement in solubility and dissolution. This combination enhanced the solubility of NTG by 23 folds. Another ternary dispersion of NTG with soluplus and gelucire 48/16 enhanced solubility by 25 fold. Conclusion: Ternary solid dispersion found superior over binary dispersions. For the ternary dispersions, showing the best solubility, tablets were prepared. Dissolution and drug release from the formulated tablet was as good as a marketed product.

Telmisartan (TEL), a type of antihypertensive drug, has poor solubility. To improve its solubility, the co-amorphous telmisartan with pimelic acid (PA) in molar ratio of 1:1 and 2:1, respectively, were obtained using a liquid-assisted grinding method. The co-amorphous system was characterized by the powder X-ray diffraction and differential scanning calorimetry. The molecular interactions of the co-amorphous were studied by the infrared spectra. After the formation of co-amorphous, the solubility of TELwas much improved, and the apparent solubility values were approximately 9-15 times as high as that of crystalline TEL. Moreover, the co-amorphous TEL-PA was stored under 25 °C/20% RH for a month without any evidence of conversion by powder X-ray diffraction analysis.

High-performance pure near-infrared organic light-emitting materials and devices with full emission over 700 nm are still rare, though urgently needed. Iridium(III) complexes have been proven to be an important class of NIR emitters. Herein, we report a new NIR homoleptic Ir(III) complex, tris[1,4-di(5-n-octylthiophen-2-yl)benzo[g]phthalazine] iridium(III) (Ir(dotbpa)3), with full emission beyond 700 nm with an iridium mass content as low as 10 wt%. Thanks to the introduction of flexible n-octyl groups, Ir(dotbpa)3 shows greatly improved solubility and excellent solution-processability in comparison with its counterpart Ir(dtbpa)3. By utilizing a multifunctional host, solution-processed NIR-OLEDs were fabricated with a simple structure of only three organic layers and they demonstrated a pure NIR emission starting from 725 nm and a peak at 850 nm with the maximum external quantum efficiency of 0.17%, which makes them the first example of pure NIR-OLEDs based on Ir(III) emitters.

Pregabalin is an anti-convulsant blockbuster chiral drug with the trade name Lyrica in its S-form. Anhydrous pregabalin (SPG) is brittle in nature and herein, we report two novel plastically bendable SPG salts with pharmaceutically acceptable coformers oxalic acid and salicylic acid. These mechanically flexible salts show improved solubility, tabletability and compressibility compared to the marketed anhydrous form.

Objective: The present study was aimed at designing of solid dispersion based pellets of curcumin (Cu) for improving its solubility. Methods: Solid dispersion (SD) of Cu was prepared by the melt method using Poloxamer 407 (Pol 407) at a different weight ratio of Cu-Pol 407 (1:2, 1:3, 1:5, 1:7, 1:10). The solid dispersion was characterised by FTIR, SEM, DSC, XRD and evaluated for saturation solubility in water, drug content and in vitro dissolution. The pellets of Cu solid dispersion were prepared by extrusion spheronization technique and optimization was performed by 32full factorial design. The pellets were evaluated for size distribution, flow properties, hardness, disintegration and in vitro drug dissolution. Results: From the phase solubility analysis, Pol 407 was selected as a Solid dispersion carrier. The formation of Cu-SD by melt method using Pol 407, was confirmed from FTIR and DSC studies. XRD studies indicated a change of Cu from crystalline to amorphous form. There was a significant increase of Cu when formulated as SD compared to plain Cu. The optimization of extrusion spheronization process revealed the significant effect of Cu-Pol 407 ratio (p

The current study was to develop a stable amorphous mirabegron complex with improved solubility, stability, and extended-release of action. HPβCD was screened as a suitable complexing agent, which exhibited an entrapment efficiency of 91.2 ± 3.4% and facilitated transformation of drug into the amorphous state. The addition of ethylcellulose extended the release of the complex by 81.4 ± 2.8% for 12 h. The influence of HPβCD and ethyl cellulose on the crystal habit of mirabegron was analyzed by XRPD, DSC, ATR FTIR and morphological behavior were analyzed by SEM. 23 Full factorial design was used to optimize the mirabegron complex. The outcomes of stability studies illustrated amorphous complex was stable for 6 months at long-term and accelerated storage conditions, where content uniformity came under the accepted range of 98–102%. Thus, HPβCD-based inclusion complex represents a futuristic approach to design mirabegron formulation with improved solubility and extended-release of action in over active bladder syndrome. Host-guest complex of HPβCD and mirabegron.

Seriniquinone was originally isolated as a melanoma-selective anti-cancer agent from a culture broth of marine bacteria. Pharmacological studies on its selectivity and unique target are ongoing. A new dihydronaphthothiophene (1) was synthesized by the biological transformation of seriniquinone using marine-derived actinomycete Streptomyces albogriseolus OM27-12, and its derivatives (2-4) were chemically synthesized. Compounds 1-4 exhibited selective cytotoxic activity against melanoma and improved solubility.

The profound efficacy of pan-BET inhibitors is well documented, but these epigenetic agents have shown pharmacology-driven toxicity in oncology clinical trials. The opportunity to identify inhibitors with an improved safety profile by selective targeting of a subset of the eight bromodomains of the BET family has triggered extensive medicinal chemistry efforts. In this article, we disclose the identification of potent and selective drug-like pan-BD2 inhibitors such as pyrazole 23 (GSK809) and furan 24 (GSK743) that were derived from the pyrrole fragment 6. We transpose the key learnings from a previous pyridone series (GSK620 2 as a representative example) to this novel class of inhibitors, which are characterized by significantly improved solubility relative to our previous research.

Background: Itraconazole is a triazole derivative and possesses structural similarities to the azole group (imidazoles and triazoles). It is a broad spectrum fungistatic. It belongs to BCS class II category i.e. it has poor solubility and high permeability. Objective: Dissolution enhancement of poorly soluble itraconazole using purified neem gum as a natural carrier via binary dispersions and other methods was studied. Topical gel formulations of binary dispersions were developed and evaluated for in vitro and in vivo antifungal activity. Methods: Five batches of solid dispersions (SD1-SD5) in various ratios of drug: neem gum were prepared by the solvent evaporation technique. Other mixtures were also prepared by kneading, cogrinding, physical mixing methods and evaluated further. Topical gel formulations were further developed and evaluated for antifungal activity (both in vitro and in vivo). Results: Equilibrium solubility studies of various mixtures indicated SD3 (1:3) as the optimum batch out of all solid dispersion batches. Equilibrium solubility studies of mixtures (KM, CGM, PM, SM) indicated significant solubility enhancement of kneading mixture in comparison to other mixtures. FTIR studies indicated no interaction of the drug to the polymer. DSC, SEM and XRD studies indicated a transition from crystalline to the amorphous state of the drug. SD3 batch showed remarkably improved dissolution characteristics (100% drug release in 1.5 h) in comparison to the pure drug (38% in 2h). Further, the topical gel of SD3 was evaluated for in vitro diffusion, in vitro and in vivo antifungal activity. Sustained drug release (53% in 24 h) was observed in SD3 based gel formulation which is significantly higher than that in comparison to pure drug based gel (30% in 24 h). The increased area of zone of inhibition of SD3 based gel indicated better antifungal activity of the SD3 gel formulation. Further histopathology examination of skin specimens indicated enhanced efficacy of SD3 based gel in comparison to pure drug based gel. Conclusion: Solid dispersion based topical gel formulation exhibits better antifungal activity in comparison to pure drug based gel.

Hemin is a potent iron supplement. A major limitation of the applicability of hemin is its extremely low aqueous solubility and bioavailability. The aim of this work is to prepare hemin nanoparticles with improved solubility. Transmission electron microscopic images showed that hemin nanoparticles with different initial concentrations of hemin (0.1 and 0.5 mg/mL) were tadpole-shaped (head of approximately 200 nm and tail of 100 nm) and sphere-shaped (50–100 nm), respectively. Moreover, hemin nanoparticles exhibited higher solubility than free hemin. The solubility of sphere-shaped nanoparticles was 308.2-fold higher than that of pure hemin at 25 °C. The hemin nanoparticles were stable in acidic conditions and displayed excellent thermal stability. These results suggested that hemin nanoparticles could serve as a potential iron supplement with potential applications in the food, biomedical, and photodynamic-photothermal therapy fields. Electronic supplementary material The online version of this article (10.1186/s11671-019-2880-7) contains supplementary material, which is available to authorized users.

The objective of this study was to formulate and optimize a stable rilpivirine nanosuspension. In the present study, yttrium stabilized zirconium oxide beads being used as the milling media in nanomilling process. The lyophilized nanocrystals were being characterized by particle size distribution (PSD), polydispersity index (PDI), X-ray diffraction (XRD) and FTIR (Fourier transform infrared spectroscopy). Optimized nanosuspension has mean particle diameter of 266 nm, PDI of 0.158, zeta potential of 22.1 mV and spherical in shape with surface oriented stabilizer molecules. Flow properties like sedimentation volume, poura-bility with the F value of 0.94 and also the redispersability even after 4 weeks of storage was found to be satisfactory for the optimized nano-suspension. Many folds increase in solubility and rate of drug release observed, The lyophilized nanocrystals retains its crystallinity after nanomilling, stable chemically with high drug content, therefore, the developed nanosuspension would be an alternative better formulation than its conventional formulation to address its bioavailability issue. However, this should be further confirmed by appropriate techniques in vivo studies.

Here we report a new and facile strategy of lignin modification with sustainable levulinic acid to introduce active ketone groups. The obtained lignin derivative exhibited significantly improved solubility and could be utilized to produce polymers such as high-performance polyimine thermosets via the Schiff base reaction with diamines.

To obtain a highly selective, direct coagulation factor Xa (FXa) inhibitor with excellent antithrombotic activity and improved solubility, a series of novel 3,4-diaminobenzoyl derivatives were designed and synthesized based on reported structure–activity relationship analysis of FXa inhibitors. Preliminary solubility test showed that the decrease of intramolecular hydrogen bonds and the change of rigid structure could effectively improve physicochemical property of compounds. The synthesized compound 7ab could significantly prolong prothrombin time at a concentration of 40 nM compared with Apixaban. Docking investigation of 7ab with FXa protein revealed that the several groups could form multiple hydrogen bonds with amino acid residues ALA-190, ASP-189 and GLY-216. These results indicated that compound 7ab might serve as a potential anticoagulant agent.

Protein aggregation is a widespread phenomenon with important implications in many scientific areas. Although amyloid formation is typically considered as detrimental, functional amyloids that perform physiological roles have been identified in all kingdoms of life. Despite their functional and pathological relevance, the structural details of the majority of molecular species involved in the amyloidogenic process remains elusive. Here, we explore the application of AlphaFold, a highly accurate protein structure predictor, in the field of protein aggregation. While we envision a straightforward application of AlphaFold in assisting the design of globular proteins with improved solubility for biomedical and industrial purposes, the use of this algorithm for predicting the structure of aggregated species seems far from trivial. First, in amyloid diseases, the presence of multiple amyloid polymorphs and the heterogeneity of aggregation intermediates challenges the "one sequence, one structure" paradigm, inherent to sequence-based predictions. Second, aberrant aggregation is not the subject of positive selective pressure, precluding the use of evolutionary-based approaches, which are the core of the AlphaFold pipeline. Instead, amyloid polymorphism seems to be constrained by the need for a defined structure-activity relationship in functional amyloids. They may thus provide a starting point for the application of AlphaFold in the amyloid landscape.

Nanotechnology has made a great impact on the pharmaceutical, biotechnology, food, and cosmetics industries. More than 40% of the approved drugs are lipophilic and have poor solubility. This is the major rate-limiting step that influences the release profile and bioavailability of drugs. Several approaches have been reported to administer lipophilic drugs with improved solubility and bioavailability. Nanotechnology plays a crucial role in the targeted delivery of poorly soluble drugs. Nanotechnology-based drug delivery systems can be classified as solid lipid nanoparticulate drug delivery systems, emulsion-based nanodrug delivery systems, vesicular drug delivery systems, etc. Nanotechnology presents a new frontier in research and development to conquer the limitations coupled with the conventional drug delivery systems through the formation of specific functionalized particles. This review presents a bird's eye view on various aspects of lipid nanoparticles as carriers of bioactive molecules that is, synthesis, characterization, advantage, disadvantage, toxicity, and application in the medical field. Update on recent development in terms of patents and clinical trials of solid lipid nanoparticles (SLNs) and nanostructure lipid carriers (NLCs) have also been discussed in this article.

Psychosis is a high-incidence pathology associated with a profound alteration in the perception of reality. The limitations of drugs available on the market have stimulated the search for alternative solutions to achieve effective antipsychotic therapies. In this review, we evaluate innovative formulations of antipsychotic drugs developed through the application of modern pharmaceutical technologies, including classes of micro and nanocarriers, such as lipid formulations, polymeric nanoparticles (NPs), solid dispersions, and cyclodextrins (CDs). We also consider alternative routes of administration to the oral and parenteral ones currently used. Improved solubility, stability of preparations, and pharmacokinetic (PK) and pharmacodynamic (PD) parameters confirm the potential of these new formulations in the treatment of psychotic disorders.

Sildenafil is a potent selective, reversible inhibitor of phosphodiesterase type 5 (PDE5) approved for the treatment of erectile dysfunction and pulmonary arterial hypertension. Whilst twenty years have passed since its original approval by the US Food and Drug Administration (USFDA), sildenafil enters the fourth industrial era catalyzing the treatment advances against erectile dysfunction and pulmonary hypertension. The plethora of detailed clinical data accumulated and the two sildenafil analogues marketed, namely tadalafil and vardenafil, signify the relevant therapeutic and commercial achievements. The pharmacokinetic and pharmacodynamic behavior of the drug appears complex, interdependent and of critical importance whereas the treatment of special population cohorts is considered. The diversity of the available formulation strategies and their compatible administration routes, extend from tablets to bolus suspensions and from per os to intravenous, respectively, inheriting the associated strengths and weaknesses. In this comprehensive review, we attempt to elucidate the multi-disciplinary elements spanning the knowledge fields of chemical synthesis, physicochemical properties, pharmacology, clinical applications, biopharmaceutical profile, formulation approaches for different routes of administration and analytical strategies, currently employed to guide the development of sildenafil-based compositions.