{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T14:00:20Z","timestamp":1793887220102,"version":"4.8.0"},"reference-count":41,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,5,11]],"date-time":"2022-05-11T00:00:00Z","timestamp":1652227200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002383","name":"King Saud University","doi-asserted-by":"publisher","award":["RSP-2021\/340"],"award-info":[{"award-number":["RSP-2021\/340"]}],"id":[{"id":"10.13039\/501100002383","id-type":"DOI","asserted-by":"publisher"}]},{"name":"RSP","award":["RSP-2021\/340"],"award-info":[{"award-number":["RSP-2021\/340"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Psoriatic arthritis is an autoimmune disease of the joints that can lead to persistent inflammation, irreversible joint damage and disability. The current treatments are of limited efficacy and inconvenient. Apremilast (APR) immediate release tablets Otezla\u00ae have 20\u201333% bioavailability compared to the APR absolute bioavailability of 73%. As a result, self-nanoemulsifying drug delivery systems (SNEDDS) of APR were formulated to enhance APR\u2019s solubility, dissolution, and oral bioavailability. The drug assay was carried out using a developed and validated HPLC method. Various thermodynamic tests were carried out on APR-SNEDDS. Stable SNEDDS were characterized then subjected to in vitro drug release studies via dialysis membrane. The optimum formulation was F9, which showed the maximum in vitro drug release (94.9%) over 24 h, and this was further investigated in in vivo studies. F9 was composed of 15% oil, 60% Smix, and 25% water and had the lowest droplet size (17.505 \u00b1 0.247 nm), low PDI (0.147 \u00b1 0.014), low ZP (\u221213.35 mV), highest %T (99.15 \u00b1 0.131) and optimum increases in the relative bioavailability (703.66%) compared to APR suspension (100%) over 24 h. These findings showed that APR-SNEDDS is a possible alternative delivery system for APR. Further studies are warranted to evaluate the major factors that influence the encapsulation efficiency and stability of APR-containing SNEDDS.<\/jats:p>","DOI":"10.3390\/molecules27103085","type":"journal-article","created":{"date-parts":[[2022,5,12]],"date-time":"2022-05-12T05:10:32Z","timestamp":1652332232000},"page":"3085","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Self-Nanoemulsifying Drug Delivery System (SNEDDS) of Apremilast: In Vitro Evaluation and Pharmacokinetics Studies"],"prefix":"10.3390","volume":"27","author":[{"given":"Ahad S.","family":"Abushal","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fadilah S.","family":"Aleanizy","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9320-0516","authenticated-orcid":false,"given":"Fulwah Y.","family":"Alqahtani","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faiyaz","family":"Shakeel","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5821-5600","authenticated-orcid":false,"given":"Muzaffar","family":"Iqbal","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"},{"name":"Central Laboratory, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nazrul","family":"Haq","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5288-5953","authenticated-orcid":false,"given":"Ibrahim A.","family":"Alsarra","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"139","DOI":"10.3389\/fendo.2017.00139","article-title":"Psoriasis, psoriatic arthritis, and thyroid autoimmunity","volume":"8","author":"Ruffilli","year":"2017","journal-title":"Front. Endocrinol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1056\/NEJMra1505557","article-title":"Psoriatic arthritis","volume":"376","author":"Ritchlin","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_3","first-page":"E70","article-title":"Psoriatic arthritis: Update on pathophysiology, assessment and management","volume":"3","author":"Mease","year":"2011","journal-title":"Ann. Rheum. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1016\/j.bcp.2012.01.001","article-title":"Apremilast mechanism of action and application to psoriasis and psoriatic arthritis","volume":"83","author":"Schafer","year":"2012","journal-title":"Biochem. Pharmacol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1007\/s40265-014-0218-4","article-title":"Apremilast: First global approval","volume":"74","author":"Poole","year":"2014","journal-title":"Drugs"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1111\/j.1529-8019.2008.01215.x","article-title":"Psoriatic arthritis","volume":"22","author":"Gladman","year":"2009","journal-title":"Dermatol. Ther."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1038\/nrrheum.2011.125","article-title":"Management of psoriatic arthritis from the view of the dermatologist","volume":"7","author":"Chang","year":"2011","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1016\/j.ijpharm.2017.03.067","article-title":"Solubility and thermodynamics of apremilast in different mono solvents: Determination, correlation and molecular interactions","volume":"523","author":"Shakeel","year":"2017","journal-title":"Int. J. Pharm."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.jiec.2017.07.002","article-title":"Solubility and thermodynamic function of apremilast in different (Transcutol + water) cosolvent mixtures: Measurement, correlation and molecular interactions","volume":"56","author":"Shakeel","year":"2017","journal-title":"J. Ind. Eng. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1248\/cpb.c16-00519","article-title":"Development of an extended-release formulation for apremilast and a level A in vitro-in vivo correlation study in Beagle dogs","volume":"64","author":"Tang","year":"2016","journal-title":"Chem. Pharm. Bull."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1587","DOI":"10.2147\/IJN.S195048","article-title":"Preparation of sustained release apremilast-loaded PLGA nanoparticles: In vitro characterization and in vivo pharmacokinetic study in rats","volume":"14","author":"Anwer","year":"2019","journal-title":"Int. J. Nanomed."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1386","DOI":"10.1080\/16583655.2020.1812269","article-title":"Formulation, characterization, in vitro and in vivo evaluations of self-nanoemulsifying drug delivery system of luteolin","volume":"180","author":"Ansari","year":"2020","journal-title":"J. Taibah Univ. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Kazi, M., Alhajri, A., Alshehri, S.M., Elzayat, E.M., Al Meanazel, O.T., Shakeel, F., Noman, O., Altamimi, M.A., and Alanazi, F.K. (2020). Enhancing oral bioavailability of apigenin using a bioactive self-nanoemulsifying drug delivery system (Bio-SNEDDS): In vitro, in vivo and stability evaluations. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12080749"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.cbi.2014.07.013","article-title":"Preparation and characterization of bionanoemulsions for improving and modulating the antioxidant efficacy of natural phenolic antioxidant curcumin","volume":"222","author":"Malik","year":"2014","journal-title":"Chem. Biol. Interact."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"591","DOI":"10.3109\/21691401.2016.1163716","article-title":"Wound healing effects of nanoemulsion containing clove essential oil","volume":"45","author":"Alam","year":"2017","journal-title":"Art. Cells Nanomed. Biotechnol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.msec.2017.03.088","article-title":"Oral bioavailability enhancement and hepatoprotective effects of thymoquinone by self-nanoemulsifying drug delivery system","volume":"76","author":"Kalam","year":"2017","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1007\/s13205-019-1630-y","article-title":"Wound healing evaluation of self-nanoemulsifying drug delivery system containing Piper cubeba essential oil","volume":"9","author":"Shakeel","year":"2019","journal-title":"3 Biotech"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Shakeel, F., Alamer, M.M., Alam, P., Alshetaili, A., Haq, N., Alanazi, F.K., Alshehri, S., Ghoneim, M.M., and Alsarra, I.A. (2021). Hepatoprotective effects of bioflavonoid luteolin using self-nanoemulsifying drug delivery system. Molecules, 26.","DOI":"10.3390\/molecules26247497"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1208\/s12249-017-0826-x","article-title":"Anticancer efficacy of self-nanoemulsifying drug delivery system of sunitinib malate","volume":"19","author":"Alshahrani","year":"2018","journal-title":"Aaps Pharmscitech"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Shakeel, F., Salem-Bekhit, M.M., Haq, N., and Alshehri, S. (2021). Nanoemulsification improves the pharmaceutical properties and bioactivities of niaouli essential oil (Malaleuca quinquenervia L.). Molecules, 26.","DOI":"10.3390\/molecules26164750"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/S0928-0987(01)00095-1","article-title":"Modeling and comparison of dissolution profiles","volume":"15","author":"Costa","year":"2001","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_22","first-page":"217","article-title":"Kinetic modeling on drug release from controlled drug delivery systems","volume":"67","author":"Dash","year":"2010","journal-title":"Acta Pol. Pharm."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1208\/s12249-009-9323-1","article-title":"In vitro characterization and mosquito (Aedes aegypti) repellent activity of essential-oils-loaded nanoemulsions","volume":"10","author":"Nuchuchua","year":"2009","journal-title":"Aaps Pharmscitech"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.4155\/bio-2016-0098","article-title":"Determination of apremilast in rat plasma by UPLC-MS\/MS in ESI-negative mode to avoid adduct ions formation","volume":"8","author":"Iqbal","year":"2016","journal-title":"Bioanalysis"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"103715","DOI":"10.1016\/j.arabjc.2022.103715","article-title":"Enhanced oral bioavailability through nanotechnology in Saudi Arabia: A meta analysis","volume":"15","year":"2022","journal-title":"Arabian. J. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"114097","DOI":"10.1016\/j.addr.2021.114097","article-title":"Oral delivery of therapeutic peptides and proteins: Technology landscape of lipid-based nanocarriers","volume":"182","author":"Haddadzadegan","year":"2022","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1007\/s40005-021-00557-5","article-title":"Effect of lipid nanoparticles on physicochemical properties, cellular uptake, and lymphatic uptake of 6-methoxflavone","volume":"52","author":"Ryu","year":"2022","journal-title":"J. Pharm. Investig."},{"key":"ref_28","first-page":"117","article-title":"Phase-solubility techniques","volume":"4","author":"Higuchi","year":"1965","journal-title":"Adv. Anal. Chem. Instr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.molliq.2016.10.017","article-title":"Self-nanoemulsifying drug delivery system of sinapic acid: In vitro and in vivo evaluation","volume":"224","author":"Shakeel","year":"2016","journal-title":"J. Mol. Liq."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.molliq.2013.01.008","article-title":"Ultra fine super self-nanoemulsifying drug delivery system (SNEDDS) enhanced solubility and dissolution of indomethacin","volume":"180","author":"Shakeel","year":"2013","journal-title":"J. Mol. Liq."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.ejpb.2006.10.014","article-title":"Development and bioavailability assessment of ramipril nanoemulsion formulation","volume":"66","author":"Shafiq","year":"2007","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.molliq.2013.03.011","article-title":"Impact of various nonionic surfactants on self-nanoemulsification efficiency of two grades of Capryol (Capryol-90 and Capryol-PGMC)","volume":"182","author":"Shakeel","year":"2013","journal-title":"J. Mol. Liq."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"106058","DOI":"10.1016\/j.ejps.2021.106058","article-title":"Development and pharmacokinetic evaluation of a self-nanoemulsifying drug delivery system for the oral delivery of cannabidiol","volume":"168","author":"Kok","year":"2022","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Ashfaq, M., Shah, S., Rasul, A., Hanif, M., Khan, H.U., Khames, A., Abdelgawad, M.A., Ghoneim, M.M., Ali, M.Y., and Abourehab, M.A.S. (2022). Enhancement of solubility and bioavailability of pitavsatatin through a self-nanoemulsifying drug delivery system (SNEDDS). Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14030482"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/j.jsps.2019.03.004","article-title":"Evaluation of the bioavailability of hydrocortisone when prepared as solid dispersion","volume":"27","author":"Altamimi","year":"2019","journal-title":"Saudi Pharm. J."},{"key":"ref_36","first-page":"806","article-title":"Potential of nanoemulsions for intravenous delivery of rifampicin","volume":"63","author":"Ahmed","year":"2008","journal-title":"Pharmazie"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"347","DOI":"10.5650\/jos.ess13213","article-title":"Enhanced antibacterial effects of clove essential oil by nanoemulsion","volume":"63","author":"Anwer","year":"2014","journal-title":"J. Oleo Sci."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Shakeel, F., Alam, P., Ali, A., Alqarni, M.H., Alshetaili, A., Ghoneim, M.M., Alshehri, S., and Ali, A. (2021). Investigating antiarthritic potential of nanostructured clove oil (Syzygium aromaticum) in FCA-induced arthritic rats: Pharmaceutical action and delivery straggles. Molecules, 26.","DOI":"10.3390\/molecules26237327"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Perween, N., Alshehri, S., Easwari, T.S., Verma, V., Faiyazuddin, M., Alanazi, A., and Shakeel, F. (2021). Investigating the feasibility of mefenamic acid nanosuspension for pediatric delivery: Preparation, characterization, and role of excipients. Processes, 9.","DOI":"10.3390\/pr9040574"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1111\/jphp.12550","article-title":"Bioavailability enhancement and pharmacokinetic profile of an anticancer drug ibrutinib by self-nanoemulsifying drug delivery system","volume":"68","author":"Shakeel","year":"2016","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.molliq.2015.06.069","article-title":"Pharmacokinetic and in vitro cytotoxic evaluation cholesterol-rich nanoemulsion of cholesteryl-succinyl-5-fluorouracil","volume":"211","author":"Shakeel","year":"2015","journal-title":"J. Mol. Liq."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/10\/3085\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:09:21Z","timestamp":1760137761000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/10\/3085"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,11]]},"references-count":41,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["molecules27103085"],"URL":"https:\/\/doi.org\/10.3390\/molecules27103085","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,11]]}}}