{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T17:14:29Z","timestamp":1793726069614,"version":"4.6.1"},"reference-count":61,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,7,26]],"date-time":"2023-07-26T00:00:00Z","timestamp":1690329600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"\u201cMinistry of Education\u201d in Saudi Arabia","award":["IFKSUOR3-129-1"],"award-info":[{"award-number":["IFKSUOR3-129-1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gels"],"abstract":"<jats:p>Oral and parenteral delivery routes of valproic acid (VA) are associated with serious adverse effects, high hepatic metabolism, high clearance, and low bioavailability in the brain. A GastroPlus program was used to predict in vivo performance of immediate (IR) and sustained release (SR) products in humans. HSPiP software 5.4.08 predicted excipients with maximum possible miscibility of the drug. Based on the GastroPlus and HSPiP program, various excipients were screened for experimental solubility, nanoemulsions, and respective gel studies intended for nasal-to-brain delivery. These were characterized by size, size distribution, polydispersity index, zeta potential, morphology, pH, % transmittance, drug content, and viscosity. In vitro drug release, ex vivo permeation profile (goat nasal mucosa), and penetration studies were conducted. Results showed that in vivo oral drug dissolution and absorption were predicted as 98.6 mg and 18.8 mg, respectively, from both tablets (IR and SR) at 8 h using GastroPlus. The predicted drug access to the portal vein was substantially higher in IR (115 mg) compared to SR (82.6 mg). The plasma drug concentration\u2013time profile predicted was in good agreement with published reports. The program predicted duodenum and jejunum as the prime sites of the drug absorption and no effect of nanonization on Tmax for sustained release formulation. Hansen parameters suggested a suitable selection of excipients. The program recommended nasal-to-brain delivery of the drug using a cationic mucoadhesive nanoemulsion. The optimized CVE6 was associated with the optimal size (113 nm), low PDI (polydispersity index) (0.26), high zeta potential (+34.7 mV), high transmittance (97.8%), and high strength (0.7% w\/w). In vitro release and ex vivo permeation of CVE6 were found to be substantially high as compared to anionic AVE6 and respective gels. A penetration study using confocal laser scanning microscopy (CLSM) executed high fluorescence intensity with CVE6 and CVE6-gel as compared to suspension and ANE6. This might be attributed to the electrostatic interaction existing between the mucosal membrane and nanoglobules. Thus, cationic nanoemulsions and respective mucoadhesive gels are promising strategies for the delivery of VA to the brain through intransal administration for the treatment of seizures and convulsions.<\/jats:p>","DOI":"10.3390\/gels9080603","type":"journal-article","created":{"date-parts":[[2023,7,27]],"date-time":"2023-07-27T02:14:48Z","timestamp":1690424088000},"page":"603","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["GastroPlus- and HSPiP-Oriented Predictive Parameters as the Basis of Valproic Acid-Loaded Mucoadhesive Cationic Nanoemulsion Gel for Improved Nose-to-Brain Delivery to Control Convulsion in Humans"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6275-5375","authenticated-orcid":false,"given":"Afzal","family":"Hussain","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4877-864X","authenticated-orcid":false,"given":"Mohammad A.","family":"Altamimi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohhammad","family":"Ramzan","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Lovely Professional University, Phagwara 144411, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohd Aamir","family":"Mirza","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tahir","family":"Khuroo","sequence":"additional","affiliation":[{"name":"PGx Global Foundation, Houston, TX 77035, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,26]]},"reference":[{"key":"ref_1","unstructured":"(2021, December 20). 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