title: Hybrid systems based on "drug - in cyclodextrin - in nanoclays" for improving oxaprozin dissolution properties.
abstract: A combined approach based on drug complexation with cyclodextrins, and complex entrapment in nanoclays has been investigated, to join in a single delivery system the benefits of these carriers and potentiate their ability to improve the dissolution properties of oxaprozin (OXA), a poorly water-soluble anti-inflammatory drug. Based on previous studies, randomly methylated ß-cyclodextrin (RAMEB) was chosen as the most effective cyclodextrin for OXA complexation. Adsorption equilibrium studies performed on three different clays (sepiolite, attapulgite, bentonite) allowed selection of sepiolite (SV) for its greater adsorption power towards OXA. DSC and XRPD studies indicated drug amorphization in both binary OXA-RAMEB coground and OXA-SV cofused products, due to its complexation or very fine dispersion in the clay structure, respectively. The drug amorphous state was maintained also in the ternary OXA-RAMEB-SV cofused system. Dissolution studies evidenced a clear synergistic effect of RAMEB complexation and clay nanoencapsulation in improving the OXA dissolution properties, with an almost 100% increase in percent dissolved and dissolution efficiency compared to the OXA-RAMEB coground system. Therefore, the proposed combined approach represents an interesting tool for improving the therapeutic effectiveness of poorly soluble drugs, and reducing the CD amount necessary for obtaining the desired drug solubility and dissolution rate increase.
authors.affiliation: Department of Chemistry, University of Florence, via Schiff 6, Sesto Fiorentino, 50019 Florence, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Mura
authors.affiliation: Department of Chemistry, University of Florence, via Schiff 6, Sesto Fiorentino, 50019 Florence, Italy. Electronic address: francesca.maestrelli@unifi.it.
authors.forename: Francesca
authors.initials: F
authors.lastname: Maestrelli
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology, University of Granada, Campus de Cartuja, s/n 18071 Granada, Spain.
authors.forename: Carola
authors.initials: C
authors.lastname: Aguzzi
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology, University of Granada, Campus de Cartuja, s/n 18071 Granada, Spain; Andalusian Institution of Earth Sciences, CSIC-University of Granada, Avda. de Las Palmeras 4, 18100, Armilla, Granada, Spain.
authors.forename: César
authors.initials: C
authors.lastname: Viseras
mesh_terms: D000538:Aluminum Silicates / Q000737:chemistry*; D000893:Anti-Inflammatory Agents / Q000737:chemistry; D001546:Bentonite / Q000737:chemistry; D000077215:Clay; D003505:Cyclodextrins / Q000737:chemistry*; D017616:Magnesium Compounds / Q000737:chemistry; D017633:Magnesium Silicates / Q000737:chemistry; D053758:Nanoparticles / Q000737:chemistry*; D000077431:Oxaprozin; D011422:Propionates / Q000737:chemistry*; D017655:Silicon Compounds / Q000737:chemistry; D012995:Solubility; D047392:beta-Cyclodextrins / Q000737:chemistry
chemical_list: D000538:Aluminum Silicates; D000893:Anti-Inflammatory Agents; D003505:Cyclodextrins; D017616:Magnesium Compounds; D017633:Magnesium Silicates; D011422:Propionates; D017655:Silicon Compounds; D047392:beta-Cyclodextrins; D001546:Bentonite; C001671:magnesium trisilicate; D000077431:Oxaprozin; D000077215:Clay; C026325:attapulgite
keywords: Clay-cyclodextrin hybrid systems; Cyclodextrin complexation; Nanoclays; Oxaprozin; Sepiolite