title: Intranasal Eutectic Powder of Zolmitriptan with Enhanced Bioavailability in the Rat Brain.
abstract: Intranasal administration can potentially deliver drugs to the brain because of the proximity of the delivery site to the olfactory lobe. We prepared triturates of micronized or crystalline zolmitriptan with a GRAS substance, nicotinamide, to form a eutectic. We characterized the formulation using differential scanning calorimetry, powder X-ray diffraction, and FTIR spectroscopy to confirm its eutectic nature and generated a phase diagram. The eutectic formulation was aerosolized using an in-house insufflator into the nares of rats. Groups of rats received zolmitriptan intravenously or intranasally, or intranasal eutectic formulation. Zolmitriptan was estimated in the olfactory lobe, cerebral cortex, cerebellum, and blood plasma at different time-points by LC-MS. Pharmacokinetics in these tissues indicated the superiority of the intranasal eutectic formulation for brain targeting when compared with results of IV solution and intranasal pure zolmitriptan powder. Enhancement of nose-to-brain transport is likely to have resulted from more rapid dissolution of the eutectic as compared to pure drug.
authors: Pharmaceutics Division, CSIR-Central Drug Research Institute , Sector 10A, Janakipuram Extension, Nauvakhera, Lucknow 226031, India.|Hygeia Institute of Pharmaceutical Education and Research , Ghazipur Balram, Ghaila Road, Lucknow 226001, India.
authors: Tabassum
authors: T
authors: Khan
authors: Pharmaceutics Division, CSIR-Central Drug Research Institute , Sector 10A, Janakipuram Extension, Nauvakhera, Lucknow 226031, India.
authors: Rajeev
authors: R
authors: Ranjan
authors: Pharmaceutics Division, CSIR-Central Drug Research Institute , Sector 10A, Janakipuram Extension, Nauvakhera, Lucknow 226031, India.
authors: Yeshwant
authors: Y
authors: Dogra
authors: Pharmaceutics Division, CSIR-Central Drug Research Institute , Sector 10A, Janakipuram Extension, Nauvakhera, Lucknow 226031, India.
authors: Sanketkumar M
authors: SM
authors: Pandya
authors: Pharmaceutics Division, CSIR-Central Drug Research Institute , Sector 10A, Janakipuram Extension, Nauvakhera, Lucknow 226031, India.|Department of Pharmaceutical Sciences, Kashmir University , Srinagar 190006, India.
authors: Hasham
authors: H
authors: Shafi
authors: Pharmaceutics Division, CSIR-Central Drug Research Institute , Sector 10A, Janakipuram Extension, Nauvakhera, Lucknow 226031, India.
authors: S K
authors: SK
authors: Singh
authors: Pharmaceutics Division, CSIR-Central Drug Research Institute , Sector 10A, Janakipuram Extension, Nauvakhera, Lucknow 226031, India.
authors: Prem N
authors: PN
authors: Yadav
authors: Pharmaceutics Division, CSIR-Central Drug Research Institute , Sector 10A, Janakipuram Extension, Nauvakhera, Lucknow 226031, India.
authors: Amit
authors: A
authors: Misra
mesh_terms: D000281:Administration, Intranasal / Q000379:methods*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002152:Calorimetry, Differential Scanning; D002851:Chromatography, High Pressure Liquid; D016503:Drug Delivery Systems / Q000379:methods*; D009297:Nasal Mucosa / Q000378:metabolism*; D023303:Oxazolidinones / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D010316:Particle Size; D051381:Rats; D017550:Spectroscopy, Fourier Transform Infrared; D053719:Tandem Mass Spectrometry; D014363:Tryptamines / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D014961:X-Ray Diffraction
chemical_list: D023303:Oxazolidinones; D014363:Tryptamines; C089750:zolmitriptan
keywords: brain delivery; eutectic; intranasal; nose-to-brain transport; zolmitriptan