title: Evaluation of submicron emulsion as vehicles for rapid-onset intranasal delivery and improvement in brain targeting of zolmitriptan.
abstract: This study was to evaluate submicron emulsion as a drug carrier for intranasal delivery of zolmitriptan (ZT). Since the drug distribution in submicron emulsion might influence the nasal absorption, two different formulations separately incorporating the drug in oily phase (ZTSE-1) and aqueous phase (ZTSE-2) were assessed. To find the better formulation for rapid-onset intranasal delivery and improvement in brain targeting of ZT, the in vivo nasal absorption of these two formulations was evaluated. The blood and cerebrospinalfluid (CSF) pharmacokinetics of ZTSE-1, ZTSE-2 and ZT solution (ZTS) were evaluated after intranasal administered to anesthetized Wistar rats. The results demonstrated that ZT from ZTSE-1 and ZTSE-2 had better brain targeting efficiency than the ZTS. In plasma and CSF, the ZTSE-2 reached peak concentration much faster than ZTSE-1 and ZTS. The ZTSE-2 also presented significantly higher initial ZT levels in CSF compared with the ZTSE-1 and ZTS. The results indicated that incorporation of ZT in the aqueous phase of submicron emulsion was effective for rapid intranasal delivery of drug to blood and brain, which would offer patients the benefits of rapid relief from migraine.
authors.affiliation: Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, China.
authors.forename: Chaoqun
authors.initials: C
authors.lastname: Yu
authors.forename: Pengfei
authors.initials: P
authors.lastname: Gu
authors.forename: Wenjun
authors.initials: W
authors.lastname: Zhang
authors.forename: Cuifang
authors.initials: C
authors.lastname: Cai
authors.forename: Haibing
authors.initials: H
authors.lastname: He
authors.forename: Xing
authors.initials: X
authors.lastname: Tang
mesh_terms: D000281:Administration, Intranasal; D000588:Amines / Q000737:chemistry; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D001921:Brain / Q000378:metabolism*; D002552:Cerebral Ventricles / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D004655:Emulsions; D005990:Glycerol / Q000737:chemistry; D007275:Injections, Intravenous; D054709:Lecithins / Q000737:chemistry; D019301:Oleic Acid / Q000737:chemistry; D023303:Oxazolidinones / Q000008:administration & dosage* / Q000097:blood / Q000134:cerebrospinal fluid* / Q000737:chemistry / Q000493:pharmacokinetics; D010316:Particle Size; D014677:Pharmaceutical Vehicles / Q000737:chemistry*; D020442:Poloxamer / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D058825:Serotonin 5-HT1 Receptor Agonists / Q000008:administration & dosage / Q000097:blood / Q000134:cerebrospinal fluid / Q000737:chemistry / Q000493:pharmacokinetics; D012995:Solubility; D055672:Static Electricity; D014280:Triglycerides / Q000737:chemistry; D014363:Tryptamines / Q000008:administration & dosage* / Q000097:blood / Q000134:cerebrospinal fluid* / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D000588:Amines; D004655:Emulsions; D054709:Lecithins; D023303:Oxazolidinones; D014677:Pharmaceutical Vehicles; D058825:Serotonin 5-HT1 Receptor Agonists; D014280:Triglycerides; D014363:Tryptamines; D020442:Poloxamer; C089750:zolmitriptan; D019301:Oleic Acid; C013173:osteum; C009317:stearylamine; D005990:Glycerol