Gavini, Elisabetta and Rassu, Giovanna and Sanna, Vanna Annunziata and Cossu, Massimo and Giunchedi, Paolo (2005) Mucoadhesive microspheres for nasal administration of an antiemetic drug, metoclopramide: in-vitro/ex-vivo studies. Journal of Pharmacy and Pharmacology, Vol. 57 (3), p. 287-294. ISSN 0022-3573. eISSN 2042-7158. Article.
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Microparticulate delivery systems designed for the nasal administration of an antiemetic drug, metoclopramide hydrochloride, were prepared. Microspheres composed of sodium alginate, chitosan hydrochloride, or both, were obtained using a spray-drying method; some batches of drug-free microparticles were prepared as a comparison. The morphology, in-vitro swelling behaviour, mucoadhesive properties and drug release from microparticles were evaluated. Ex-vivo drug permeation tests were carried out using sheep nasal mucosa; permeation test of the drug solution was peformed as comparison. During ex-vivo permeation tests, transmission electron microscopy (TEM) analyses were carried out on the nasal mucosa to study the morphological changes of epithelial cells and tight junctions, while the change in microsphere morphology was examined using photostereo microscopy (PM). Spray-dried microparticles had a mean diameter (dvs) in the range of about 3–10 μm. They showed good in-vitro mucoadhesive properties. In-vitro release profiles and swelling behaviour depended on their composition: the drug release occurred in 1–3 h. Ex-vivo studies showed that drug permeation through the mucosa from microparticles based on chitosan was higher than from those consisting of alginate alone. This can be related to the penetration enhancing properties of chitosan. Complexation of chitosan with alginate led to a control of the drug release. Microscopy observation of microspheres during the permeation tests revealed that microparticles swelled and gelled, maintaining their shape. TEM analyses of the mucosa after exposure to the microparticles consisting of alginate/chitosan showed opened tight junctions. This preliminary study shows that alginate/chitosan spray-dried microspheres have promising properties for use as mucoadhesive nasal carriers of an antiemetic drug.
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