Screening of Mucoadhesive Microparticles Containing Hydroxypropyl- Beta-Cyclodextrin for the Nasal Delivery of Risperidone

Mario      Jug; Mira      Becirevic-Lacan

Abstract

Interaction of the antipsychotic drug risperidone with hydroxypropyl-beta-cyclodextrin (HPBCD) in solution and in the solid state was studied with the aim of overcoming the limitations associated with nasal administration of low solubility drugs. Risperidone solubility studies revealed inclusion complex formation with a 1:1 stoichiometry. Low concentrations (0.1 w/v %) of hydroxypropylmethyl cellulose (HPMC) and carbomer affected risperidone solubility in water. No formation of a ternary complex was detected. The solid inclusion complex was prepared by spray drying and was characterised by thermal (DSC) and spectral (FTIR) analyses. Risperidone and the inclusion complex were loaded into microparticles by spray drying using HPMC, carbomer and HPMC/carbomer interpolymer complex (IPC) as mucoadhesive components. The microparticles were characterised with respect to drug loading, particle size distribution, thermal analysis, and zeta potential measurements. Mucoadhesive properties of the microparticles were studied by measuring the work of adhesion. Carbomer and IPC based microparticles revealed superior mucoadhesive microparticles compared to HPMC based microparticles. Drug incorporation into microparticles reduced their mucoadhesive properties, while incorporation of the cyclodextrin complex caused no additional reduction in mucoadhesion. The in vitro dissolution studies showed that formation of the inclusion complex significantly increased the risperidone dissolution rate from the microparticles, thus providing sustained drug release.

Keywords: Risperidone, hydroxypropyl-beta-cyclodextrin, nasal administration, mucoadhesive microparticles, hydroxypropylmethyl cellulose, carbomer, interpolymer complex

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