Clinical Efficacy and Patient Outcomes

It is therefore important for you to note that the information contained in this article does not constitute professional medical or healthcare advice, diagnosis or recommendation of treatment and is not intended to, nor should be used to, replace professional medical advice. This article may not always be up to date and is not exhaustive of all of the risks and considerations relevant to this particular drug. In no circumstances should this article be relied upon without independent consideration and confirmation by a qualified medical practitioner. Your doctor will be able to explain all possible uses, dosages, precautions, interactions with other drugs, and other potential adverse effects, and you should always talk to them about any kind of medication you are taking, thinking about taking or wanting to stop taking. DescriptionDosage FormOral SuspensionIndicationPulmonary Arterial hypertensionBrand NameRevatio®TE CodeABLactoseNoGlutenNoColorOff-White to Light Yellow PowderShapeNAMarkingsNAStorage ConditionBEFORE RECONSTITUTION: Store below 30°C (86°F) in the original package in order to protect from moisture.

AFTER RECONSTITUTION: Store below 30°C (86°F) or in refrigerator at 2°C to 8°C (36°F to 46°F) Do not freeze.

How should this medicine be used?

In amorphous systems, drugs and carriers are completely dissolved in tablet sildenafil 50 mg organic solvents and spray-dried. As a result, the physicochemical properties of the drug were changed, thereby the oral bioavailability increased.16 In contrast, crystalline systems are generated using distilled water as a solvent. The use of distilled water allows free from the residual organic solvent issue. Furthermore, improved oral bioavailability of the drug was achieved without alteration of physicochemical properties.17,18 Self-nanoemulsifying drug delivery systems (SNEDDS) are composed of oil, surfactant and co-surfactant.19,20 When water penetrates drug-loaded SNEDDS, oil-in-water (o/w) nanoemulsions are naturally created. These nano-sized emulsions have a large surface area in contact with water, which increases the solubility of the drug.

Indications and Usage for Sildenafil Oral Suspension

Likewise, o/w nanoemulsion is formed in the gastrointestinal (GI) tract, when drug-loaded SNEDDS is mixed with GI fluid. Furthermore, oil exerts permeation enhancement, resulting in increased absorption in the GI tract.21–23 To improve convenience and stability, porous inorganic carriers are usually added and spray dried for producing solid SNEDDS.24 For these reasons, solid SNEDDS has been widely studied for improving oral bioavailability of poorly water-soluble drugs, these days. Recently, amorphous microspheres, crystalline microspheres and solid SNEDDS are three representative drug delivery systems for improving the oral bioavailability of poorly water-soluble drugs. Therefore, in order to increase the aqueous solubility and oral bioavailability of sildenafil the most, those three representative techniques must be compared. Additionally, this is the first study that has compared microspheres and solid SNEDDS in order to improve the oral bioavailability of sildenafil, till date. Discard any unused portion 60 days after reconstitution.PACK SIZE: “112 mL following ReconstitutionNDC#: 27241-0175-29Click to View Package Insert Click to View Material Data Safety Sheet Revatio ® is registered trademark of Pfizer Back to Journals » International Journal of Nanomedicine » Volume 16 Comparison of Three Different Aqueous Microenvironments for Enhancing Oral Bioavailability of Sildenafil: Solid Self-Nanoemulsifying Drug Delivery System, Amorphous Microspheres and Crystalline Microspheres Authors Kim JS , Din FU , Lee SM, Kim DS, Woo MR, Cheon S, Ji SH, Kim JO, Youn YS , Oh KT , Lim SJ, Jin SG , Choi HG Editor who approved publication: Dr Yan Shen Jung Suk Kim,1,* Fakhar ud Din,2,* Sang Min Lee,1,* Dong Shik Kim,1 Mi Ran Woo,1 Seunghyun Cheon,1 Sang Hun Ji,1 Jong Oh Kim,3 Yu Seok Youn,4 Kyung Taek Oh,5 Soo-Jeong Lim,6 Sung Giu Jin,7 Han-Gon Choi1 1College of Pharmacy, Hanyang University, Ansan, South Korea; 2Department of Pharmacy, Quaid-I-Azam University, Islamabad, Pakistan; 3College of Pharmacy, Yeungnam University, Gyongsan, South Korea; 4School of Pharmacy, Sungkyunkwan University, Suwon, South Korea; 5College of Pharmacy, Chung-Ang University, Seoul, South Korea; 6Department of Bioscience and biotechnology, Sejong University, Seoul, South Korea; 7Department of Pharmaceutical Engineering, Dankook University, Cheonan, South Korea*These authors contributed equally to this workCorrespondence: Sung Giu Jin; Han-Gon Choi Tel +82 41-550-3558; +82 31-400-5802Fax +82 41-559-7945; +82 31-400-5958Email [email protected]; [email protected]Background: The purpose of this study was to screen various drug delivery systems for improving the aqueous solubility and oral bioavailability of sildenafil.

Three representative techniques, solid self-nanoemulsifying drug delivery systems (SNEDDS), amorphous microspheres and crystalline microspheres, were compared.Methods: Both microspheres systems contained sildenafil:Labrasol:PVP at a weight ratio of 1:1:6.

Key takeawaysAI

The solidification process in SNEDDS was performed using HDK N20 Pharma as a solid carrier.Results: The amorphous microspheres appeared spherical with significantly decreased particle size compared to the drug powder. The crystalline microspheres exhibited a rough surface with no major particle-size difference compared with sildenafil powder, indicating that the hydrophilic excipients adhered to the sildenafil crystal. Solid SNEDDS presented a smooth surface, assuming that the oily liquid was adsorbed to the porous solid carrier. According to the physicochemical evaluation, the crystalline state maintained in crystalline microspheres, whereas the crystal state changed to amorphous state in other formulations. Amorphous microspheres, crystalline microspheres and solid SNEDDS produced about 79, 55, 82-fold increased solubility, compared to drug powder.

Aqueous Solubility and Dissolution Profile of Prepared Sildenafil-Loaded Formulations

Moreover, the prepared formulations provided a higher dissolution rate (%) and plasma concentration than did the drug powder (performance order; solid SNEDDS ≥ amorphous microspheres ≥ crystalline microspheres > drug powder). Among the formulations, solid SNEDDS demonstrated the highest improvement in oral bioavailability (AUC; 1508.78 ± 343.95 h·ng/mL).Conclusion: Therefore, solid SNEDDS could be recommended as an oral dosage form for enhancing the oral bioavailability of sildenafil.Keywords: sildenafil, amorphous microspheres, crystalline microspheres, solid self-nanoemulsifying drug delivery system, aqueous microenvironment, oral bioavailability Sildenafil reversibly inhibits the phosphodiesterase-5 enzyme and is clinically used for the treatment of erectile dysfunction.1 Moreover, sildenafil induces pulmonary vasodilation and promotes gas exchange in the lung; and hence, it has been prescribed to patients with pulmonary arterial hypertension.2,3 Sildenafil possesses inadequate aqueous solubility. It is reported that drugs with low aqueous solubility are precipitated when in contact with gastrointestinal fluid. The precipitated drugs hardly permeate intestinal lumen, resulting in poor oral bioavailability.4,5 The citrate form has been the most common technique to enhance the solubility of sildenafil.6–8 However, salt forms lack lipophilic properties, reducing permeability through the gastrointestinal membrane, thereby decreasing oral bioavailability.9 Therefore, in the present study, various drug delivery techniques other than salt formation were studied for improving the aqueous solubility and oral bioavailability of sildenafil. Developing microspheres is one of the representative solubilising technologies.10,11 In the microspheres system, poorly water-soluble drugs are disseminated in hydrophilic excipients giving spherical shape with micrometre size.12 Microspheres are produced by utilising various methods such as spray-drying and hot melt extrusion.13,14 The former method is prepared by dissolving/suspending drugs and ingredients in proper solvent.15 Depending on the type of solvent, microspheres system can be classified into amorphous and crystalline system. The amorphous microspheres were manufactured using ethanol, while crystalline microspheres were generated using distilled water. Liquid SNEDDS was composed of sildenafil:Labrasol:Transcutol HP:Captex 300 in the ratio of 1:70:15:15 (w:w:w:w).

Why is this medication prescribed?

The solidification process in SNEDDS was performed using HDK N20 Pharma as a solid carrier.Results: The amorphous microspheres appeared spherical with significantly decreased particle size compared to the drug powder. The crystalline microspheres exhibited a rough surface with no major particle-size difference compared with sildenafil powder, indicating that the hydrophilic excipients adhered to the sildenafil crystal. Solid SNEDDS presented a smooth surface, assuming that the oily liquid was adsorbed to the porous solid carrier. According to the physicochemical evaluation, the crystalline state maintained in crystalline microspheres, whereas the crystal state changed to amorphous state in other formulations.

Amorphous microspheres, crystalline microspheres and solid SNEDDS produced about 79, 55, 82-fold increased solubility, compared to drug powder. Moreover, the prepared formulations provided a higher dissolution rate (%) and plasma concentration than did the drug powder (performance order; solid SNEDDS ≥ amorphous microspheres ≥ crystalline microspheres > drug powder).

Data availability statement

Spray-dryer was used to fabricate each drug delivery system. Spray-drying was chosen due to its widespread use in pharmaceutical industry and laboratory-scale experiments.25–27 Compared to other techniques, such as supercritical fluid-based approach or microfluidics, spray-dryer has several advantages including continuous mode of operation, reproducibility and low production cost.28–30 Amorphous microspheres, crystalline microspheres and solid SNEDDS were compared according to aqueous solubility, dissolution profile and physicochemical properties. The schematic design of this study is illustrated in Figure 1. Each physicochemical property was expected to induce different solubilising mechanisms and aqueous microenvironments.31 These differences resulted in performance order in aqueous solubility, according to the previous studies.32 Moreover, pharmacokinetic studies in rats were conducted to compare the oral bioavailability of sildenafil among amorphous microspheres, crystalline microspheres, solid SNEDDS and drug powder. Finally, a drug delivery system exhibiting the highest oral bioavailability of sildenafil was selected.

Less common

Sildenafil (base) was supplied by Huons Pharm. Polyvinylpyrrolidone (PVP, K30), Solutol HS15 and Cremophor EL were purchased from BASF (Ludwigshafen, Germany). Dextran, polyvinyl alcohol (PVA), hydroxypropyl methylcellulose 2910 (HPMC), pyrogenic silica (HDK N20 Pharma), hydroxypropyl cellulose low viscosity (HPC-L), carboxymethyl cellulose sodium (Na-CMC), poloxamer 188, PEG 4000 and hydroxypropyl beta-cyclodextrin (HP-β-CD) were kindly offered from Hanmi Pharm. Soybean oil, sorbitan monooleate (Span 80), olive oil, polysorbate (Tween 80) and corn oil were provided by Daejung Chem. Among the formulations, solid SNEDDS demonstrated the highest improvement in oral bioavailability (AUC; 1508.78 ± 343.95 h·ng/mL).Conclusion: Therefore, solid SNEDDS could be recommended as an oral dosage form for enhancing the oral bioavailability of sildenafil.Keywords: sildenafil, amorphous microspheres, crystalline microspheres, solid self-nanoemulsifying drug delivery system, aqueous microenvironment, oral bioavailability Sildenafil reversibly inhibits the phosphodiesterase-5 enzyme and is clinically used for the treatment of erectile dysfunction.1 Moreover, sildenafil induces pulmonary vasodilation and promotes gas exchange in the lung; and hence, it has been prescribed to patients with pulmonary arterial hypertension.2,3 Sildenafil possesses inadequate aqueous solubility. It is reported that drugs with low aqueous solubility are precipitated when in contact with gastrointestinal fluid.

• Common side effects include headache, flushing, and dizziness.
• Allergic reactions are rare but require immediate medical attention.
• Effects usually last for 4 to 6 hours.

The precipitated drugs hardly permeate intestinal lumen, resulting in poor oral bioavailability.4,5 The citrate form has been the most common technique to enhance the solubility of sildenafil.6–8 However, salt forms lack lipophilic properties, reducing permeability through the gastrointestinal membrane, thereby decreasing oral bioavailability.9 Therefore, in the present study, various drug delivery techniques other than salt formation were studied for improving the aqueous solubility and oral bioavailability of sildenafil.

Supplemental material

Developing microspheres is one of the representative solubilising technologies.10,11 In the microspheres system, poorly water-soluble drugs are disseminated in hydrophilic excipients giving spherical shape with micrometre size.12 Microspheres are produced by utilising various methods such as spray-drying and hot melt extrusion.13,14 The former method is prepared by dissolving/suspending drugs and ingredients in proper solvent.15 Depending on the type of solvent, microspheres system can be classified into amorphous and crystalline system. In amorphous systems, drugs and carriers are completely dissolved in tablet sildenafil 50 mg organic solvents and spray-dried. As a result, the physicochemical properties of the drug were changed, thereby the oral bioavailability increased.16 In contrast, crystalline systems are generated using distilled water as a solvent. The use of distilled water allows free from the residual organic solvent issue.

Furthermore, improved oral bioavailability of the drug was achieved without alteration of physicochemical properties.17,18 Self-nanoemulsifying drug delivery systems (SNEDDS) are composed of oil, surfactant and co-surfactant.19,20 When water penetrates drug-loaded SNEDDS, oil-in-water (o/w) nanoemulsions are naturally created. These nano-sized emulsions have a large surface area in contact with water, which increases the solubility of the drug. Likewise, o/w nanoemulsion is formed in the gastrointestinal (GI) tract, when drug-loaded SNEDDS is mixed with GI fluid.

Other uses for this medicine

It is therefore important for you to note that the information contained in this article does not constitute professional medical or healthcare advice, diagnosis or recommendation of treatment and is not intended to, nor should be used to, replace professional medical advice. This article may not always be up to date and is not exhaustive of all of the risks and considerations relevant to this particular drug. In no circumstances should this article be relied upon without independent consideration and confirmation by a qualified medical practitioner. Your doctor will be able to explain all possible uses, dosages, precautions, interactions with other drugs, and other potential adverse effects, and you should always talk to them about any kind of medication you are taking, thinking about taking or wanting to stop taking. DescriptionDosage FormOral SuspensionIndicationPulmonary Arterial hypertensionBrand NameRevatio®TE CodeABLactoseNoGlutenNoColorOff-White to Light Yellow PowderShapeNAMarkingsNAStorage ConditionBEFORE RECONSTITUTION: Store below 30°C (86°F) in the original package in order to protect from moisture.

Sildenafil Oral Sublingual Spray Manufacturer, Exporter, and Supplier in India

AFTER RECONSTITUTION: Store below 30°C (86°F) or in refrigerator at 2°C to 8°C (36°F to 46°F) Do not freeze. Discard any unused portion 60 days after reconstitution.PACK SIZE: “112 mL following ReconstitutionNDC#: 27241-0175-29Click to View Package Insert Click to View Material Data Safety Sheet Revatio ® is registered trademark of Pfizer Back to Journals » International Journal of Nanomedicine » Volume 16 Comparison of Three Different Aqueous Microenvironments for Enhancing Oral Bioavailability of Sildenafil: Solid Self-Nanoemulsifying Drug Delivery System, Amorphous Microspheres and Crystalline Microspheres Authors Kim JS , Din FU , Lee SM, Kim DS, Woo MR, Cheon S, Ji SH, Kim JO, Youn YS , Oh KT , Lim SJ, Jin SG , Choi HG Editor who approved publication: Dr Yan Shen Jung Suk Kim,1,* Fakhar ud Din,2,* Sang Min Lee,1,* Dong Shik Kim,1 Mi Ran Woo,1 Seunghyun Cheon,1 Sang Hun Ji,1 Jong Oh Kim,3 Yu Seok Youn,4 Kyung Taek Oh,5 Soo-Jeong Lim,6 Sung Giu Jin,7 Han-Gon Choi1 1College of Pharmacy, Hanyang University, Ansan, South Korea; 2Department of Pharmacy, Quaid-I-Azam University, Islamabad, Pakistan; 3College of Pharmacy, Yeungnam University, Gyongsan, South Korea; 4School of Pharmacy, Sungkyunkwan University, Suwon, South Korea; 5College of Pharmacy, Chung-Ang University, Seoul, South Korea; 6Department of Bioscience and biotechnology, Sejong University, Seoul, South Korea; 7Department of Pharmaceutical Engineering, Dankook University, Cheonan, South Korea*These authors contributed equally to this workCorrespondence: Sung Giu Jin; Han-Gon Choi Tel +82 41-550-3558; +82 31-400-5802Fax +82 41-559-7945; +82 31-400-5958Email [email protected]; [email protected]Background: The purpose of this study was to screen various drug delivery systems for improving the aqueous solubility and oral bioavailability of sildenafil. Three representative techniques, solid self-nanoemulsifying drug delivery systems (SNEDDS), amorphous microspheres and crystalline microspheres, were compared.Methods: Both microspheres systems contained sildenafil:Labrasol:PVP at a weight ratio of 1:1:6. The amorphous microspheres were manufactured using ethanol, while crystalline microspheres were generated using distilled water. Liquid SNEDDS was composed of sildenafil:Labrasol:Transcutol HP:Captex 300 in the ratio of 1:70:15:15 (w:w:w:w). Furthermore, oil exerts permeation enhancement, resulting in increased absorption in the GI tract.21–23 To improve convenience and stability, porous inorganic carriers are usually added and spray dried for producing solid SNEDDS.24 For these reasons, solid SNEDDS has been widely studied for improving oral bioavailability of poorly water-soluble drugs, these days. Recently, amorphous microspheres, crystalline microspheres and solid SNEDDS are three representative drug delivery systems for improving the oral bioavailability of poorly water-soluble drugs. Therefore, in order to increase the aqueous solubility and oral bioavailability of sildenafil the most, those three representative techniques must be compared.

• Sildenafil oral solution can interact with nitrates and certain medications.
• Always inform your doctor of all medicines being taken.
• Failure to do so can cause serious adverse effects.

Additionally, this is the first study that has compared microspheres and solid SNEDDS in order to improve the oral bioavailability of sildenafil, till date. Spray-dryer was used to fabricate each drug delivery system. Spray-drying was chosen due to its widespread use in pharmaceutical industry and laboratory-scale experiments.25–27 Compared to other techniques, such as supercritical fluid-based approach or microfluidics, spray-dryer has several advantages including continuous mode of operation, reproducibility and low production cost.28–30 Amorphous microspheres, crystalline microspheres and solid SNEDDS were compared according to aqueous solubility, dissolution profile and physicochemical properties. The schematic design of this study is illustrated in Figure 1.

• The cost of sildenafil oral solution varies depending on brand and pharmacy.
• Generic versions are typically less expensive.
• Availability might be limited in some regions or countries.

Each physicochemical property was expected to induce different solubilising mechanisms and aqueous microenvironments.31 These differences resulted in performance order in aqueous solubility, according to the previous studies.32 Moreover, pharmacokinetic studies in rats were conducted to compare the oral bioavailability of sildenafil among amorphous microspheres, crystalline microspheres, solid SNEDDS and drug powder. Finally, a drug delivery system exhibiting the highest oral bioavailability of sildenafil was selected. Sildenafil (base) was supplied by Huons Pharm. Polyvinylpyrrolidone (PVP, K30), Solutol HS15 and Cremophor EL were purchased from BASF (Ludwigshafen, Germany).

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Dextran, polyvinyl alcohol (PVA), hydroxypropyl methylcellulose 2910 (HPMC), pyrogenic silica (HDK N20 Pharma), hydroxypropyl cellulose low viscosity (HPC-L), carboxymethyl cellulose sodium (Na-CMC), poloxamer 188, PEG 4000 and hydroxypropyl beta-cyclodextrin (HP-β-CD) were kindly offered from Hanmi Pharm. Soybean oil, sorbitan monooleate (Span 80), olive oil, polysorbate (Tween 80) and corn oil were provided by Daejung Chem.