Development of in vitro models to demonstrate the ability of PecSys (R), an in situ nasal gelling technology, to reduce nasal run-off and drip

作者：Castile Jonathan^*; Cheng Yu Hui; Simmons Ben; Perelman Michael; Smith Alan; Watts Peter

来源：Drug Development and Industrial Pharmacy, 2013, 39(5): 816-824.

DOI：10.3109/03639045.2012.707210

• Nasal drug delivery
• pectin
• formulation
• no-drip
• gels
• in situ gelling
• inclined plate
• anatomical nasal cast
• in vitro models
• mucosal drug delivery

Many of the increasing number of intranasal products available for either local or systemic action can be considered sub-optimal, most notably where nasal drip or run-off give rise to discomfort/tolerability issues or reduced/variable efficacy. PecSys, an in situ gelling technology, contains low methoxy (LM) pectin which gels due to interaction with calcium ions present in nasal fluid. PecSys is designed to spray readily, only forming a gel on contact with the mucosal surface. The present study employed two in vitro models to confirm that gelling translates into a reduced potential for drip/run-off: (i) Using an inclined TLC plate treated with a simulated nasal electrolyte solution (SNES), mean drip length [+/- SD, n = 10] was consistently much shorter for PecSys (1.5 +/- 0.4 cm) than non-gelling control (5.8 +/- 1.6 cm); (ii) When PecSys was sprayed into a human nasal cavity cast model coated with a substrate containing a physiologically relevant concentration of calcium, PecSys solution was retained at the site of initial deposition with minimal redistribution, and no evidence of run-off/drip anteriorly or down the throat. In contrast, non-gelling control was significantly more mobile and consistently redistributed with run-off towards the throat. Conclusion: In both models PecSys significantly reduced the potential for run-off/drip ensuring that more solution remained at the deposition site. In vivo, this enhancement of retention will provide optimum patient acceptability, modulate drug absorption and maximize the ability of drugs to be absorbed across the nasal mucosa and thus reduce variability in drug delivery.

• 出版日期2013-5