In situ gelling, bioadhesive nasal inserts for extended drug delivery: In vitro characterization of a new nasal dosage form

The purpose of this study was the preparation and characterization of sponge-like, in situ gelling inserts based on bioadhesive polymers. Hydrophilic polymers (carrageenan, Carbopol, chitosan, hydroxypropyl methylcellulose (HPMC) K15M and ES, sodium alginate, sodium carboxy methylcellulose (NaCMC), polyvinyl pyrrolidone (PVP) 90, xanthan gum) were dissolved with/without the model drug oxymetazoline HCl in demineralized water and lyophilized into small inserts. The drug release, water uptake, mechanical properties, X-ray diffraction and bioadhesion potential of the nasal inserts were investigated. A sponge-like structure of nasal inserts was formed with amorphous, but not with crystalline polymers during the freeze-drying process. The insert hardness increased with the glass transition temperature of the polymer (PVP25 < PVP30 < PVP90). The bioadhesion potential was governed by the polymer ability to interact with mucin/agar (highest for carrageenan, Carbopol, xanthan gum and NaCMC). Inserts prepared from low molecular weight polymers resulted in polymer dissolution and fast drug release (HPMC ES, Na-alginate, PVP90). The drug release from inserts prepared from high molecular weight polymers (carrageenan, Carbopol, chitosan, HPMC K15M, NaCMC, xanthan gum) was a complex interplay of osmotic forces, water uptake and electrostatic interactions between drug and polymer. The drug release decreased with higher polymer content and increased drug loading of the insert. Bioadhesive nasal inserts have a high potential as new nasal dosage form for extended drug delivery. (c) 2005 Elsevier B.V. All rights reserved.