title: Vancomycin-triacetyl cyclodextrin interaction products for prolonged drug delivery.
abstract: The aim of the present work was to investigate the capability of vancomycin (VCM) to interact with three hydrophobic cyclodextrins (TACD) (triacetyl alpha-, beta-, or gamma cyclodextrin) and the role played by the preparation technique in the formation of interaction products aimed at prolonging drug delivery for site-specific treatment of bone infections. Physical mixtures of VCM with triacetyl alpha-, beta-, or gamma-cyclodextrin in a 1:1 molar ratio were subjected to kneading, coevaporation, and spray drying from aqueous suspensions or hydroacetonic solution. Thermal behavior (TG, DSC), percent drug content (HPLC), and drug release (Franz cell) of VCM from the physical mixtures, and the relevant binary systems obtained by the various complexation methods were evaluated. All binary systems were characterized by having a particle size compatible with parenteral site-specific administration and with drug-loading efficiencies close to 100%, thus indicating the stability of vancomycin toward each and every complexation process. In vitro drug release measurements showed that the preparation technique plays a different role depending on the type of cyclodextrin used. In the kneading process, the binary system containing TAalphaCD is the most efficient in slowing down the VCM release. With the coevaporation technique, the system based on TAbetaCD was most effective in prolonging drug release. None of the triacetyl-cyclodextrins is suitable in prolonging VCM release upon spray drying from aqueous suspensions, because this preparation technique does not determine drug-cyclodextrin interaction. On the other hand, spray drying from hydroacetonic solutions always results in a reduction in drug release, linked to the formation of VCM-TACD interaction products and is particularly pronounced for the VCM-TAgammaCD interaction product. The unique properties of prolonging drug release and maintaining the antimicrobial activity of the native drug render such an interaction product the most promising candidate in the development of delivery systems intended for parenteral site-specific administration of VCM.
authors.affiliation: Department of Pharmaceutical Chemistry, University of Pavia, Pavia, Italy.
authors.forename: Franca
authors.initials: F
authors.lastname: Ferrari
authors.forename: Milena
authors.initials: M
authors.lastname: Sorrenti
authors.forename: Silvia
authors.initials: S
authors.lastname: Rossi
authors.forename: Laura
authors.initials: L
authors.lastname: Catenacci
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Sandri
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Bonferoni
authors.forename: Carla
authors.initials: C
authors.lastname: Caramella
authors.forename: Giampiero
authors.initials: G
authors.lastname: Bettinetti
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology; D003505:Cyclodextrins / Q000737:chemistry*; D003692:Delayed-Action Preparations; D003890:Desiccation; D004055:Differential Thermal Analysis; D004339:Drug Compounding; D016983:Enterococcus / Q000187:drug effects; D005079:Excipients; D008826:Microbial Sensitivity Tests; D010316:Particle Size; D013211:Staphylococcus aureus / Q000187:drug effects; D013696:Temperature; D014640:Vancomycin / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D003505:Cyclodextrins; D003692:Delayed-Action Preparations; D005079:Excipients; D014640:Vancomycin