Solid-state characterization and dissolution profiles of the inclusion complexes of omeprazole with native and chemically modified β-cyclodextrin

被引:116
作者
Figuelras, Ana
Carvalho, Rul A.
Ribeiro, Laura
Torres-Labandeira, Juan J.
Veiga, Francisco J. B.
机构
[1] Univ Coimbra, Pharmaceut Technol Lab, Coimbra, Portugal
[2] Univ Coimbra, Pharmacol Studies Ctr, Coimbra, Portugal
[3] Univ Coimbra, Dept Biochem, Coimbra, Portugal
[4] Univ Santiago de Compostela, Pharmaceut Technol Lab, Santiago De Compostela, Spain
关键词
omeprazole; beta-cyclodextrin; methyl-beta-cyclodextrin; physicochemical characterization; dissolution profile; inclusion complex;
D O I
10.1016/j.ejpb.2007.03.005
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The aim of this work was to investigate the formation of the inclusion complex between omeprazole (OME), a benzimidazolic derivative and a methylated cyclodextrin, methyl-beta-cyclodextrin (M beta CD), with an average degree of substitution of 0.5. Inclusion complex between OME and beta-cyclodextrin (beta CD), a natural cyclodextrin, was used as reference. In aqueous media, apparent stability constants (K-s), which describe the extent of formation of the complexes, have been determined by UV spectroscopy and H-1 NMR experiments. The stoichiometry of the complexes was found to be 1: 1 mol:mol OME:cyclodextrin (CD) and the value of Ks was higher for OME:M beta CD than for OME:beta CD inclusion complexes. Solid binary systems of OME and CDs were prepared by different techniques, namely kneading, spray-drying and freeze-drying. The formation and physicochemical characterization of solid inclusion complexes were investigated by differential scanning calorimetry (DSC), Fourier transform-infrared (FTIR), X-ray diffractometry (XRD) and scanning electron microscopy (SEM). The results show that freeze-drying method produces true inclusion complexes between OME and both CDs. In contrast, crystalline drug was detectable in kneaded and spray-drying products. The dissolution of OME from the binary systems was studied to select the most appropriate system for the development of a buccal drug delivery formulation. It was concluded that the preparation technique played an important role in the dissolution behaviour of the drug and the inclusion complex between OME and M beta CD obtained by spray-drying and freeze-drying allowed better performances. (C) 2007 Elsevier B.V. All rights reserved.
引用
收藏
页码:531 / 539
页数:9
相关论文
共 36 条
[1]  
[Anonymous], PHARM TECHNOL INT
[2]   Study of omeprazole-γ-cyclodextrin complexation in the solid state [J].
Arias, MJ ;
Moyano, JR ;
Muñoz, P ;
Ginés, JM ;
Justo, A ;
Giordano, F .
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY, 2000, 26 (03) :253-259
[3]   Thermodynamics of inclusion complexes of natural and modified cyclodextrins with propranolol in aqueous solution at 298 K [J].
Castronuovo, Gluseppina ;
Niccoli, Marcella .
BIOORGANIC & MEDICINAL CHEMISTRY, 2006, 14 (11) :3883-3887
[4]   Cyclodextrins in drug delivery: An updated review [J].
Challa, R ;
Ahuja, A ;
Ali, J ;
Khar, RK .
AAPS PHARMSCITECH, 2005, 6 (02)
[5]   Differential scanning calorimetry: applications in drug development [J].
Clas, SD ;
Dalton, CR ;
Hancock, BC .
PHARMACEUTICAL SCIENCE & TECHNOLOGY TODAY, 1999, 2 (08) :311-320
[6]   Utility of nuclear magnetic resonance spectroscopy to characterize the structure of dexamethasone sodium phosphate inclusion complexes with cyclodextrins in solution and to analyze potential competitive effects [J].
Echezarreta-López, MM ;
Perdomo-López, I ;
Estrada, E ;
Vila-Jato, JL ;
Torres-Labandeira, JJ .
JOURNAL OF PHARMACEUTICAL SCIENCES, 2002, 91 (06) :1536-1547
[7]   Physicochemical characterization and in vitro dissolution behavior of nicardipine-cyclodextrins inclusion compounds [J].
Fernandes, CM ;
Vieira, MT ;
Veiga, FJB .
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES, 2002, 15 (01) :79-88
[8]  
FIGUEIRAS A, 2006, PHARM RES
[9]   High-performance liquid chromatographic assay for methyl-beta-cyclodextrin in plasma and cell lysate [J].
Grosse, PY ;
Pinguet, F ;
Joulia, JM ;
Astre, C ;
Bressolle, F .
JOURNAL OF CHROMATOGRAPHY B, 1997, 694 (01) :219-226
[10]  
Higuchi T., 1965, Interscience, New York, V4, P117