Intranasal Eutectic Powder of Zolmitriptan with Enhanced Bioavailability in the Rat Brain

• DOI: 10.1021/acs.molpharmaceut.6b00453
• Publication Date: 2016-08-12T13:55:06Z
• Authors: Tabassum Khan; Rajeev Ranjan; Yeshwant Dogra; Sanketkumar M. Pa...; Hasham Shafi; S. K. Singh; Prem N. Yadav; Amit Misra
• Keywords: Calorimetry, Differential Scanning; Brain; Tryptamines; Rats; 3. Good health; Nasal Mucosa; 03 medical and health sciences; Drug Delivery Systems; 0302 clinical medicine; X-Ray Diffraction; Tandem Mass Spectrometry; Spectroscopy, Fourier Transform Infrared; Animals; Particle Size; Administration, Intranasal; Chromatography, High Pressure Liquid; Oxazolidinones

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.