title: Complexation of the interferon inducer, bropirimine, with hydroxypropyl-beta-cyclodextrin.
abstract: Bropirimine (ABPP) is an orally active immunomodulator that increases endogenous alpha-interferon and other cytokines used clinically against carcinoma in situ of the bladder. The oral absorption of ABPP is poor because its low solubility in water. The purpose of this study is to develop a technological procedure useful to increase the water solubility of ABPP. To this end, the interaction of ABPP with several cyclodextrin derivatives-alpha-, beta-, gamma- and hydroxypropyl-beta-cyclodextrin with a degree of substitution 2.7 (HPbetaCD) was studied and the effect of the complexation process on the water solubility of the drug was evaluated. The best results were obtained with the hydroxypropyl derivative, HPbetaCD, that interacts in a 1:1 drug:cyclodextrin molar ratio. The inclusion complex ABPP-HPbetaCD was characterized in solution by nuclear magnetic resonance (1H-NMR). The solid inclusion complex was obtained by freeze-drying and characterized by differential scanning calorimetry (DSC), X-ray diffractometry and mass spectrometry. The dissolution rate of ABPP from the HPbetaCD solid inclusion complex was increased compared to the powdered drug but not differences were found between the complex and a physical mixture with a similar molar ratio. The increase of the dissolution rate of the drug can be attributed to the breakdown in solution of the drug dimers in the presence of the cyclodextrin and to the complex formation.
authors.affiliation: Departamento de Farmacia e Tecnoloxía Farmacéutica, Universidade de Santiago de Compostela, Facultade de Farmacia, Campus Universitario Sur, E-15706, Santiago de Compostela, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Echezarreta-López
authors.forename: J J
authors.initials: JJ
authors.lastname: Torres-Labandeira
authors.forename: L
authors.initials: L
authors.lastname: Castiñeiras-Seijo
authors.forename: L
authors.initials: L
authors.lastname: Santana-Penín
authors.forename: J L
authors.initials: JL
authors.lastname: Vila-Jato
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D003505:Cyclodextrins / Q000737:chemistry*; D003596:Cytosine / Q000031:analogs & derivatives* / Q000737:chemistry; D007369:Interferon Inducers / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular; D012995:Solubility; D014961:X-Ray Diffraction; D047391:alpha-Cyclodextrins; D047392:beta-Cyclodextrins; D047408:gamma-Cyclodextrins
chemical_list: D003505:Cyclodextrins; D007369:Interferon Inducers; D047391:alpha-Cyclodextrins; D047392:beta-Cyclodextrins; D047408:gamma-Cyclodextrins; C479658:hydroxypropyl-alpha-cyclodextrin; C479659:hydroxypropyl-gamma-cyclodextrin; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D003596:Cytosine; C033560:bropirimine