Randa Latif1, Rana R Makar2, Ehab A Hosni3, Omaima N El Gazayerly1. 1. Faculty of Pharmacy, Cairo University, Cairo, Egypt. 2. Faculty of Pharmacy, Ahram Canadian University, Cairo, Egypt. 3. Faculty of Pharmacy, Al-Kut University, Wasit, Iraq.
Abstract
OBJECTIVE: The present work focuses on improving zaleplon (ZAP) performance through nanosizing its insoluble particles which were then delivered intranasally in powder form. SIGNIFICANCE: Since nanopowders have an exceptional ability to cross cell membrane, their absorption is facilitated in the solid form. Hence, delivering insoluble ZAP nanocrystals (NC) through intranasal route improves its bioavailability due to both nanosization and the escape of hepatic metabolism. METHODS: Nanocrystals were prepared by anti-solvent precipitation followed by probe sonication in presence of Soluplus®, Poloxamer-188 (0.25%), sodium lauryl sulfate (0.5%), and mannitol. Physicochemical evaluation of the prepared NC was done by DSC and XRPD. TGA was performed for stability detection. Ex vivo permeation study through isolated cattle nasal mucosal membrane, in addition to an in vivo bioavailability study was performed for assessment of the prepared NC. RESULTS: Nanosization to 200 nm contributed to the enhancement in dissolution ∼100% within 30 min and reduced half-life to 1.63 min. Confirmation of adsorption of polymers over NC' surface was elucidated. TGA confirmed their thermal stability. Ex vivo permeation study showed a 2.7 enhancement ratio in favor of the prepared NC. Both the extent and rate of NC absorption through nasal mucosa of rabbits were significantly higher (p ˂ .05) than in case of oral tablets. The relative bioavailability of NC was increased 3.14 times as compared to the Sleep aid® tablets. CONCLUSION: The intranasal delivery of nanoscale ZAP powder proved to be a successful alternative to oral formulations that suffer poor absorption and limited bioavailability.
OBJECTIVE: The present work focuses on improving zaleplon (ZAP) performance through nanosizing its insoluble particles which were then delivered intranasally in powder form. SIGNIFICANCE: Since nanopowders have an exceptional ability to cross cell membrane, their absorption is facilitated in the solid form. Hence, delivering insoluble ZAP nanocrystals (NC) through intranasal route improves its bioavailability due to both nanosization and the escape of hepatic metabolism. METHODS: Nanocrystals were prepared by anti-solvent precipitation followed by probe sonication in presence of Soluplus®, Poloxamer-188 (0.25%), sodium lauryl sulfate (0.5%), and mannitol. Physicochemical evaluation of the prepared NC was done by DSC and XRPD. TGA was performed for stability detection. Ex vivo permeation study through isolated cattle nasal mucosal membrane, in addition to an in vivo bioavailability study was performed for assessment of the prepared NC. RESULTS: Nanosization to 200 nm contributed to the enhancement in dissolution ∼100% within 30 min and reduced half-life to 1.63 min. Confirmation of adsorption of polymers over NC' surface was elucidated. TGA confirmed their thermal stability. Ex vivo permeation study showed a 2.7 enhancement ratio in favor of the prepared NC. Both the extent and rate of NC absorption through nasal mucosa of rabbits were significantly higher (p ˂ .05) than in case of oral tablets. The relative bioavailability of NC was increased 3.14 times as compared to the Sleep aid® tablets. CONCLUSION: The intranasal delivery of nanoscale ZAP powder proved to be a successful alternative to oral formulations that suffer poor absorption and limited bioavailability.
Entities:
Keywords:
Nanocrystals; bioavailability; intranasal delivery; poorly water soluble drugs; zaleplon