Nasal drug delivery of a mucoadhesive oxybutynin chloride gel: In vitro evaluation and in vivo in situ study in experimental rats

摘要

Nasal drug delivery (NDD) is a promising approach for rapid-onset delivery to circumvent first-pass elimination when taken orally. The feasibility of developing an efficacious nasal formulation of oxybutynin chloride (OXB) has been investigated as its oral bioavailability does not exceed 6 %. Mucoadhesive nasal gels of OXB were prepared using many mucoadhesive polymers: hydroxypropyl cellulose (HPC) 1 %, carbopol 934P (CBP) 0.5 %, and methyl cellulose (MC) 1.5 % and the release profiles were evaluated in vitro. Therefore, further optimization of nasal absorption of the formula containing 1 % HPC as gel base was studied using several chemical enhancers as potential nasal drug absorption optimizers: betacyclodextrin (β-CD) 1.8 %, EDTA 0.5 % and bile salts 0.5 % were evaluated for in vivo in situ model. EDTA significantly enhanced drug paracellular transport across the nasal mucosal membrane and bile salts significantly enhanced drug absorption by both transcellular and paracellular pathways.