Multicomponent complexes of piroxicam with cyclodextrins and hydroxypropyl methylcellulose.
The purpose of the study was to investigate the effect of hydroxypropyl methylcellulose (HPMC) on the complexation of piroxicam (PX) with beta-cyclodextrin (beta-CD) and dimethyl-beta-cyclodextrin (DM-beta-CD) in solution and in the solid state. Phase solubility study revealed a positive effect of the polymer on the drug complexation. Improvement in stability constants values, Ks, of ternary complexes clearly proves the benefit of the HPMC addition for promoting higher complexation efficiency. Solid binary and ternary complexes were prepared by spray drying. Drug-CD and drug-CD-polymer interactions were studied in the solid state by differential scanning calorimetry (DSC), zeta-potential measurements, and particle size distribution. A marked increase in the PX dissolution rate was observed even in binary and ternary complexes. The presence of HPMC in ternary complexes slightly retarded the release of PX. Cyclodextrin complexation increased the PX concentration gradient over the semipermeable membrane, resulting in an increased PX flux. The retarded diffusion of PX to the membrane interface decreased the PX flux values of the ternary complexes.
Jug
Mario
M
Department of Pharmaceutics, Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia.
Bećirević-Laćan
Mira
M
D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods; D045424:Complex Mixtures / Q000737:chemistry* / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics; D065347:Hypromellose Derivatives; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000493:pharmacokinetics; D010894:Piroxicam / Q000737:chemistry* / Q000493:pharmacokinetics; D012995:Solubility; D012996:Solutions / Q000737:chemistry / Q000493:pharmacokinetics; D014867:Water; D047392:beta-Cyclodextrins / Q000737:chemistry* / Q000493:pharmacokinetics
D045424:Complex Mixtures; D004337:Drug Carriers; D012996:Solutions; D047392:beta-Cyclodextrins; D014867:Water; D010894:Piroxicam; D065347:Hypromellose Derivatives; C038119:heptakis(2,6-O-dimethyl)beta-cyclodextrin; D008747:Methylcellulose