title: Influence of hydrophilic polymers on the complexation of carbamazepine with hydroxypropyl-β-cyclodextrin.
abstract: In this study binary carbamazepine-hydroxypropyl-β-cyclodextrin, as well as ternary carbamazepine-hydroxypropyl-β-cyclodextrin-hydrophilic polymer systems were used to improve dissolution rate of carbamazepine. It has been shown that addition of hydrophilic polymers (Soluplus® and two types of hydroxypropyl methylcellulose-Metolose® 90SH-100 and Metolose® 65SH-1500) significantly increased solubilization capacity of hydroxypropyl-β-cyclodextrin for carbamazepine. Evaluation of carbamazepine-hydroxypropyl-β-cyclodextrin-hydrophilic polymer interactions using molecular modeling techniques showed interactions between carbamazepine, which dissociates from inclusion complexes and hydroxypropyl methylcellulose that can prevent crystallization of dissolved carbamazepine. These results can contribute to better understanding of drug-cyclodextrin-hydrophilic polymer interactions which are still not well understood. After evaluation of carbamazepine solubilization with hydroxypropyl-β-cyclodextrin and hydrophilic polymers, both binary carbamazepine-hydroxypropyl-β-cyclodextrin and ternary carbamazepine-hydroxypropyl-β-cyclodextrin-hydrophilic polymer systems were prepared by spray drying. The results of solid state characterization methods showed amorphous nature of carbamazepine in all spray dried systems, which together with the results of molecular modeling techniques indicates inclusion complex formation. Carbamazepine dissolution rate was significantly improved from spray dried formulations compared to pure drug. Binary carbamazepine-hydroxypropyl-β-cyclodextrin and ternary carbamazepine-hydroxypropyl-β-cyclodextrin-Soluplus® systems exhibited the fastest carbamazepine release, wherein the entire amount of carbamazepine was released during first 5 min.
authors.affiliation: Department of Pharmaceutical Technology and Cosmetology, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia. Electronic address: djordje.medarevic@pharmacy.bg.ac.rs.
authors.forename: Djordje
authors.initials: D
authors.lastname: Medarević
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.
authors.forename: Kyriakos
authors.initials: K
authors.lastname: Kachrimanis
authors.affiliation: Department of Pharmaceutical Technology and Cosmetology, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia.
authors.forename: Zorica
authors.initials: Z
authors.lastname: Djurić
authors.affiliation: Department of Pharmaceutical Technology and Cosmetology, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Ibrić
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D002220:Carbamazepine / Q000737:chemistry*; D065546:Drug Liberation; D057927:Hydrophobic and Hydrophilic Interactions; D065347:Hypromellose Derivatives / Q000737:chemistry*; D008958:Models, Molecular; D011092:Polyethylene Glycols / Q000737:chemistry*; D011145:Polyvinyls / Q000737:chemistry*; D012995:Solubility; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D011145:Polyvinyls; D047392:beta-Cyclodextrins; C572167:polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D002220:Carbamazepine; D065347:Hypromellose Derivatives; D011092:Polyethylene Glycols
keywords: Carbamazepine; Cyclodextrins; Dissolution rate enhancement; Drug–cyclodextrin–polymer interactions; Molecular dynamics simulation; Poorly soluble drugs