{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T08:30:35Z","timestamp":1776328235171,"version":"3.50.1"},"reference-count":32,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,11,4]],"date-time":"2020-11-04T00:00:00Z","timestamp":1604448000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004396","name":"Thailand Research Fund","doi-asserted-by":"publisher","award":["PHA610372S"],"award-info":[{"award-number":["PHA610372S"]}],"id":[{"id":"10.13039\/501100004396","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Sildenafil citrate is used to treat mild to moderate erectile dysfunction and premature ejaculation. However, it has low oral bioavailability, numerous adverse effects, and delayed onset of action. These problems may be resolved by transdermal delivery to the penis. Hence, sildenafil citrate was formulated as a microemulsion system using isopropyl myristate, Tween 80, PEG400, and water (30:20:40:10). The hydrogel used in the microemulsion was 2% w\/w poloxamer 188. The sildenafil microemulsion-loaded hydrogels were characterised for their appearance, particle size, pH, spreadability, swelling index, viscosity, sildenafil drug content, membrane permeation, epithelial cell cytotoxicity, and in vitro drug metabolism. The optimised formulated microemulsion showed the lowest droplet size and highest solubility of sildenafil citrate. The in vitro skin permeation of the sildenafil citrate microemulsion-loaded hydrogel was significantly higher than that of the sildenafil suspension, with a 1.97-fold enhancement ratio. The formulated microemulsion exhibited a 100% cell viability, indicating its safety for skin epithelial cells. The major metabolic pathway of sildenafil citrate loaded in the microemulsion formulation was hydroxylation. Furthermore, loading sildenafil in the microemulsion reduced the drug metabolite by approximately 50% compared to the sildenafil in aqueous suspension. The sildenafil citrate-loaded isopropyl myristate-based microemulsion hydrogels were physically and chemically stable over 6 months of storage. The sildenafil citrate microemulsion-loaded hydrogel showed in vitro results suitable for used as a transdermal drug delivery system.<\/jats:p>","DOI":"10.3390\/pharmaceutics12111055","type":"journal-article","created":{"date-parts":[[2020,11,5]],"date-time":"2020-11-05T00:00:37Z","timestamp":1604534437000},"page":"1055","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Development of a Sildenafil Citrate Microemulsion-Loaded Hydrogel as a Potential System for Drug Delivery to the Penis and Its Cellular Metabolic Mechanism"],"prefix":"10.3390","volume":"12","author":[{"given":"Apichart","family":"Atipairin","sequence":"first","affiliation":[{"name":"Drug and Cosmetics Excellence Center, Walailak University, Thasala, Nakhon Si Thammarat 80161, Thailand"},{"name":"School of Pharmacy, Walailak University, Thasala, Nakhon Si Thammarat 80161, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charisopon","family":"Chunhachaichana","sequence":"additional","affiliation":[{"name":"Drug Delivery System Excellence Center and Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkhla 90112, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Titpawan","family":"Nakpheng","sequence":"additional","affiliation":[{"name":"Drug Delivery System Excellence Center and Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkhla 90112, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Narumon","family":"Changsan","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Rangsit University, Pathumtani 12000, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teerapol","family":"Srichana","sequence":"additional","affiliation":[{"name":"Drug Delivery System Excellence Center and Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkhla 90112, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4845-1527","authenticated-orcid":false,"given":"Somchai","family":"Sawatdee","sequence":"additional","affiliation":[{"name":"Drug and Cosmetics Excellence Center, Walailak University, Thasala, Nakhon Si Thammarat 80161, Thailand"},{"name":"School of Pharmacy, Walailak University, Thasala, Nakhon Si Thammarat 80161, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,4]]},"reference":[{"key":"ref_1","first-page":"3196","article-title":"Fabrication, appraisal, and transdermal permeation of sildenafil citrate-loaded nanostructured lipid carriers versus solid lipid nanoparticles","volume":"6","author":"Elnaggar","year":"2011","journal-title":"Int. J. Nanomed."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/j.urology.2005.09.002","article-title":"Comparison of efficacy of sildenafil-only, sildenafil plus topical emla cream, and topical emla-cream-only in treatment of premature ejaculation","volume":"67","author":"Atan","year":"2006","journal-title":"Urology"},{"key":"ref_3","first-page":"289","article-title":"A double-blind placebo-controlled evaluation of the effect of topical sildenafil on erectile dysfunction","volume":"5","author":"Yonessi","year":"2005","journal-title":"J. Appl. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.3109\/10717544.2015.1077291","article-title":"Transdermal delivery of tadalafil using a novel formulation","volume":"23","author":"Baek","year":"2016","journal-title":"Drug Deliv."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"108571","DOI":"10.1016\/j.biopha.2019.01.032","article-title":"Efficacy and dermal toxicity analysis of sildenafil citrate based topical hydrogel formulation against traumatic wounds","volume":"112","author":"Kulshrestha","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_6","first-page":"199","article-title":"Pharmaceutical studies on the availability of sildenafil citrate from certain topical delivery systems","volume":"7","author":"Osman","year":"2016","journal-title":"Int. J. Pharm. Pharm. Res."},{"key":"ref_7","first-page":"102","article-title":"Formulation and evaluation of transdermal gel of sildenafil citrate","volume":"1","author":"Patel","year":"2012","journal-title":"Int. J. Pharm. Res. Allied Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/j.urology.2005.09.032","article-title":"Adjunctive use of androgel (testosterone gel) with sildenafil o treat erectile dysfunction in men with acquired androgen deficiency syndrome after failure using sildenafil alone","volume":"67","author":"Rosenthal","year":"2006","journal-title":"Urology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1208\/s12249-009-9213-6","article-title":"Intranasal microemulsion of sildenafil citrate: In vitro evaluation and in vivo pharmacokinetic study in rabbits","volume":"10","author":"Elshafeey","year":"2009","journal-title":"AAPS Pharmscitech"},{"key":"ref_10","first-page":"4131","article-title":"Use of transdermal gel of sildenafil citrate in sexual dysfunction","volume":"3","author":"Patel","year":"2012","journal-title":"Int. J. Pharm. Sci. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"563","DOI":"10.2478\/v10007-012-0031-0","article-title":"Formulation development of an albendazole self-emulsifying drug delivery system (SEDDS) with enhanced systemic exposure","volume":"62","author":"Meena","year":"2012","journal-title":"Acta Pharm."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"138","DOI":"10.22159\/ijap.2018v10i5.27415","article-title":"Preparation and evaluation of microemulsion containg antihypertensive drug","volume":"10","author":"Yadev","year":"2018","journal-title":"Int. J. Appl. Pharm"},{"key":"ref_13","first-page":"158","article-title":"Combination of synthetic and natural polymers in hydrogel: An impact on drug permeation","volume":"6","author":"Biswa","year":"2016","journal-title":"J. Appl. Pharm."},{"key":"ref_14","first-page":"77","article-title":"Formulation and evaluation of microemulsion based topical hydrogel containing lornoxicam","volume":"4","author":"Biswal","year":"2014","journal-title":"J. Appl. Pharm."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2103","DOI":"10.1208\/s12249-018-1010-7","article-title":"Thermosensitive poloxamer407\/poly(acrylic acid) hydrogels with potential application as injectable drug delivery system","volume":"19","author":"Boonlai","year":"2018","journal-title":"AAPS Pharmscitech"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.ijpharm.2013.07.023","article-title":"Sildenafil citrate monohydrate-cyclodextrin nanosuspension complexes for use in metered-dose inhalers","volume":"455","author":"Sawatdee","year":"2013","journal-title":"Int. J. Pharm."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/10837450.2017.1281952","article-title":"Enhanced dissolution of sildenafil citrate as dry foam tablets","volume":"24","author":"Sawatdee","year":"2019","journal-title":"Pharm. Dev. Technol."},{"key":"ref_18","unstructured":"(2018, April 07). Asean Guideline on Stability Study of Drug Product. Available online: https:\/\/asean.org\/wp-content\/uploads\/2018\/01\/25PPWG-ANNEX-7-iv-Final-ASEAN-Guideline-on-Stability-Study-Drug-Product-R2.pdf."},{"key":"ref_19","first-page":"1323","article-title":"Optimixed nano-transfersomal films for enhanced sildenafil citrate transdermal delivery: Ex vivo and in vivo evaluation","volume":"10","author":"Ahmed","year":"2016","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Serrano, D.R., Gordo, M.J., Matji, A., Gonz\u00e1lez, S., Lalatsa, A., and Torrado, J.J. (2019). Tuning the transdermal delivery of hydroquinone upon formulation with novel permeation enhancers. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11040167"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"567","DOI":"10.3109\/00498254.2011.563877","article-title":"Rapid-onset sildenafil nasal spray carried by microemulsion systems: In vitro evaluation and in vivo pharmacokinetic studies in rabbits","volume":"41","author":"Lu","year":"2011","journal-title":"Xenobiotica"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1007\/s12272-011-0313-y","article-title":"Comparison of the solubility and pharmacokinetics of sildenafil salts","volume":"34","author":"Jung","year":"2011","journal-title":"Arch. Pharm. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1504\/IJNT.2011.041443","article-title":"Sildenfil citrate nanoemulsion vs. self-nanoemulsifying delivery systems; rational development and transdermal permeation","volume":"8","author":"Elnaggar","year":"2011","journal-title":"Int. J. Nanotechnol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1943","DOI":"10.1080\/10717544.2018.1523256","article-title":"Effects of solvents and penetration enhancers on transdermal delivery of thymoquinone: Permeability and skin deposition study","volume":"25","author":"Haq","year":"2018","journal-title":"Drug Deliv."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2140","DOI":"10.1002\/jps.10469","article-title":"Physical properties of sildenafil citrate (Viagra) and sildenafil base","volume":"92","author":"Melnikov","year":"2003","journal-title":"J. Pharm. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1016\/j.jsps.2015.01.019","article-title":"Why sildenafil and sildenafil citrate monohydrate crystals are not stable?","volume":"23","author":"Sawatdee","year":"2015","journal-title":"Saudi Pharm. J."},{"key":"ref_27","unstructured":"Pavia, D.L., Lampman, G.M., and Kriz, G.S. (2001). Introduction to Spectroscopy: A Guide for Students of Organic Chemistry, Thomson Learning. [3rd ed.]."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Russo, E., and Villa, C. (2019). Poloxamer hydrogels for biomedical applications. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11120671"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"12415","DOI":"10.3390\/molecules181012415","article-title":"Mechanical, rheological and release behaviors of a poloxamer 407\/poloxamer 188\/Carbopol 940 thermosensitive composite hydrogel","volume":"18","author":"Chen","year":"2013","journal-title":"Molecules"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.ijpharm.2006.02.015","article-title":"Microemulsion-based hydrogel formulation of ibuprofen for topical delivery","volume":"315","author":"Chen","year":"2006","journal-title":"Int. J. Pharm."},{"key":"ref_31","first-page":"965280","article-title":"Effect of chemical enhancers in transdermal permeation of alfuzosin hydrochloride","volume":"2012","author":"Prasanthi","year":"2012","journal-title":"Int. Sch. Res. Netw. ISRN Pharm."},{"key":"ref_32","first-page":"339","article-title":"Sildenafil citrate","volume":"27","author":"Badwin","year":"2001","journal-title":"Anal. Profiles Drug Subst."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/12\/11\/1055\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:29:13Z","timestamp":1760178553000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/12\/11\/1055"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,4]]},"references-count":32,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2020,11]]}},"alternative-id":["pharmaceutics12111055"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics12111055","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,4]]}}}