{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T03:12:46Z","timestamp":1791947566580,"version":"4.3.4"},"reference-count":58,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,8,14]],"date-time":"2023-08-14T00:00:00Z","timestamp":1691971200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008809","name":"deanship of scientific research at the University of Hail","doi-asserted-by":"publisher","award":["RG 21015"],"award-info":[{"award-number":["RG 21015"]}],"id":[{"id":"10.13039\/501100008809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Chronic stable angina pectoris is the primary indication for ranolazine (RZ), an anti-anginal drug. The drug has an anti-ischemic action that is unaffected by either blood pressure or heart rate. Due to the first-pass effect, the drug has a reduced bioavailability of 35 to 50%. The study emphasized developing a novel transdermal drug delivery system of nanostructured lipid carriers (NLCs) for delivering RZ. Many pharmaceutical companies employ lipid nanoparticles as biocompatible carriers for medicinal, cosmetic, and biochemical uses. These carriers are appropriate for many applications, such as topical, transdermal, parenteral, pulmonary, and oral administration, because of the large variety of lipids and surfactants that are readily available for manufacturing. RZ NLCs were made using high-pressure homogenization. Statistical analysis was utilized to find the best formula by varying the concentrations of Precirol ATO 5 (X1), oleic acid (X2), and Tween 80 (X3). Variables such as entrapment effectiveness (EE) (Y1), particle size (Y2), polydispersity index (PDI) (Y3), and zeta potential (Y4) were tested. A variety of tests were performed on the new formulation to ascertain how well it would be absorbed in the body. These tests included in vivo absorption studies, skin permeability assessments, in vitro drug release assessments, and physicochemical analyses. The particle size of RZ-NLCs was shown to be very small (118.4 \u00b1 5.94 nm), with improved EE (88.39 \u00b1 3.1%) and low ZP and PDI (\u221241.91 \u00b1 0.38 and 0.118 \u00b1 0.028). SEM and TEM analysis confirmed the structure of the NLCs and showed a smooth, spherical surface. Improved RZ-NLCs were used to create NLC gel, which was then tested for elasticity both physically and rheologically. The formulation\u2019s elasticity was investigated. Optimized RZ-NLCs and NLCG were found to have transdermal fluxes of 48.369 g\/cm2\/h and 38.383 g\/cm2\/h, respectively. These results showed that the transdermal delivery of RZ distribution through NLC\u2019s transdermal gel had more significant potential. According to in vivo experiments, the drug\u2019s bioavailability in Wistar rats increased when it was delivered through NLCs. The findings demonstrated that NLCs loaded with RZ successfully transported the RZ to the designated site with no interruptions and that a quadratic connection existed between the independent and dependent variables.<\/jats:p>","DOI":"10.3390\/ph16081151","type":"journal-article","created":{"date-parts":[[2023,8,14]],"date-time":"2023-08-14T10:13:57Z","timestamp":1692008037000},"page":"1151","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Nanostructured Lipid Carriers to Enhance the Bioavailability and Solubility of Ranolazine: Statistical Optimization and Pharmacological Evaluations"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1080-4542","authenticated-orcid":false,"given":"Aziz","family":"Unnisa","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, University of Ha\u2019il, Ha\u2019il 81442, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4359-7145","authenticated-orcid":false,"given":"Ananda K.","family":"Chettupalli","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Center for Nanomedicine, School of Pharmacy, Anurag 10 University, Venkatapur, Ghatkesar, Medchal, Hyderabad 500088, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reem S.","family":"Alazragi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, College of Science, University of Jeddah, Jeddah 21959, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walla","family":"Alelwani","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, College of Science, University of Jeddah, Jeddah 21959, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azzah M.","family":"Bannunah","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, Umm Al-Qura University, Makkah 24382, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jameel","family":"Barnawi","sequence":"additional","affiliation":[{"name":"Department of Medical Lab Technology, Prince Fahd Bin Sultan Research Chair, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk 71491, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Padmanabha R.","family":"Amarachinta","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Center for Nanomedicine, School of Pharmacy, Anurag 10 University, Venkatapur, Ghatkesar, Medchal, Hyderabad 500088, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suresh B.","family":"Jandrajupalli","sequence":"additional","affiliation":[{"name":"Department of Preventive Dental Sciences, College of Dentistry, University of Ha\u2019il, Ha\u2019il 81442, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Badria A.","family":"Elamine","sequence":"additional","affiliation":[{"name":"Department of Radiology, College of Applied Medical Sciences, University of Ha\u2019il, Ha\u2019il 81442, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omkalthoum A.","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Department of Special Education, College of Education, University of Ha\u2019il, Ha\u2019il 81442, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Talib","family":"Hussain","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, University of Ha\u2019il, Ha\u2019il 81442, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,14]]},"reference":[{"key":"ref_1","unstructured":"Maton, A. 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