Physicochemical properties and dissolution studies of dexamethasone acetate-beta-cyclodextrin inclusion complexes produced by different methods.
Inclusion complexes between dexamethasone acetate (DMA), a poorly water soluble drug, and beta-cyclodextrin (betaCD) were obtained to improve the solubility and dissolution rate of this drug. Phase-solubility profile indicated that the solubility of DMA was significantly increased in the presence of betaCD (33-fold) and was classified as A(L)-type, indicating the 1:1 stoichiometric inclusion complexes. Solid complexes prepared by different methods (kneading, coevaporation, freeze drying) and physical mixture were characterized by differential scanning calorimetry, thermogravimetry, infrared absorption and optical microscopy. Preparation methods influenced the physicochemical properties of the products. The dissolution profiles of solid complexes were determined and compared with those DMA alone and their physical mixture, in three different mediums: simulated gastric fluid (pH 1.2), simulated intestinal fluid (pH 7.4) and distilled water. The dissolution studies showed that in all mediums DMA presented an incomplete dissolution even in four hours. In contrast, the complexes formed presented a higher dissolution rate in simulated gastric fluid (SGF pH 1.2), which indicate that these have different ionization characteristics. According to the results, the freeze-dried and kneaded products exhibited higher dissolution rates than the drug alone, in all the mediums.
Doile
Mayara M
MM
Departamento de Farmácia, Universidade da Região de Joinville, Bom Retiro, CEP 88040-900, Joinville, Santa Catarina, Brazil.
Fortunato
Keila A
KA
Schmücker
Iára C
IC
Schucko
Sacha K
SK
Silva
Marcos A S
MA
Rodrigues
Patrik O
PO
D003907:Dexamethasone / Q000031:analogs & derivatives* / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D004353:Drug Evaluation, Preclinical; D005750:Gastric Juice / Q000737:chemistry*; D008422:Materials Testing; D012995:Solubility; D047392:beta-Cyclodextrins / Q000737:chemistry*
D004337:Drug Carriers; D047392:beta-Cyclodextrins; D003907:Dexamethasone; C018038:dexamethasone acetate; C031215:betadex