Super disintegrating oromucosal nanofiber patch of zolmitriptan for rapid delivery and efficient brain targeting

Oromucosal administration of zolmitriptan using electrospun nanofiber can potentially result in blood plasma concentrations analogous to intravenous kinetics and targeting the brain due to anatomical features of the delivery site. Herein, we report the optimization of zolmitriptan and polyvinylpyrrolidone nanofibers using a Quality by Design approach. Fourier transform infrared spectroscopy, and Thermogravimetric analysis ruled out any physical and/or chemical interaction between the drug and excipient. Diffraction studies revealed a sharp decrease in the crystalline index of pure zolmitriptan from 85.75% to 8.35%.

Likely, calorimetry studies show a sharp decline in the enthalpy of fusion from 126.4 J/g before electrospinning to 67.24 J/g post electrospinning, demonstrating amorphization of the drug. The disintegration of nanofiber occurs within less than a second, and about 82% of the medicament was released in 60 s in an in vitro test, compared to 67% from the Zomig Rapimelt® tablet. Rapid drug flux of 22.07 and 22.62 μg/cm²/h occurred when nanofiber patches were applied to buccal and soft palate mucosa in an ex vivo permeability test. Biocompatibility studies established that the nanofiber patches were neither toxic nor irritating to the oral epithelium. Groups of rabbits received the zolmitriptan solution intravenously and orally, or optimized nanofibers were applied to the buccal and soft palate mucosa.

Pharmacokinetic analysis in blood plasma indicated similar kinetics of oromucosal patches and intravenous administration. More importantly, concentrations achieved in the hindbrain after administration of the patch over the soft palatal mucosa produce significantly higher concentrations than buccal or IV administration (>2-folds). The drug targeting these brain regions likely resulted from rapid dissolution, enhanced permeation, amorphization, and specialized drug transport via a trigeminal nose base-pons-medullary axis.

Material

Polyvinylpyrrolidone (PVP K30; Assay 95.54 % pure based on carbon content) was purchased from Sigma-Aldrich, St. Louis, Missouri, USA. Zolmitriptan (CAS No. 139264–17-8; Purity = >98.0% by HPLC) and rizatriptan benzoate (CAS No. 145202–66-0; Purity = >98.0% by HPLC) were procured from Tokyo Chemical Industries, Japan. HPLC grade solvents, methanol, and acetonitrile were supplied by Merck, Darmstadt, Germany.

Hasham Shafi, Rumaisa Rashid, Sami-ullah Rather, D.V. Siva Reddy, Lubna Azmi, Abdalla Abdal-hay, Salman H. Alrokayan, Haseeb A Khan, Nisar Ahmad Khan, Faheem A. Sheikh, Super disintegrating oromucosal nanofiber patch of zolmitriptan for rapid delivery and efficient brain targeting, Chemical Engineering Journal, Volume 463, 2023, 142481, ISSN 1385-8947, https://doi.org/10.1016/j.cej.2023.142481.

See also the following article to “Tablet Excipients – Disintegrant”: