β-cyclodextrin complexes of celecoxib: Molecular-modeling, characterization, and dissolution studies

Abstract

INTRODUCTIONCelecoxib, 4-[5-(4-methylphenyl)-3-trifluoromethyl-1H-pyrazol-1yl] benzene sulphonamide, is a 1,5-diarylsubstituted pyrazole with a pK a of 11.1 (Figure 1). Celecoxib was the first specific inhibitor of cycloxygenase-2 (COX-2) to be approved by the United States Food and Drug Administration (FDA), in 1998. This clinical introduction of celecoxib has been the result of the important discovery of the COX isoenzymes and the subsequent search for molecules effective in selectively inhibiting COX-2 with little or no effect on COX-1. The major clinical goal was to produce a nonsteroidal antiinflammatory drug (NSAID) that had little or no effect on the gastrointestinal (GI) tract and kidney. 1 Celecoxib is used in the treatment of rheumatoid arthritis, osteoarthritis, and for the management of the pain of these conditions.2-4 The aqueous solubility of celecoxib is low at 3 to 7 μg/mL when determined in vitro at pH 7 and 40°C. Since the pK a of celecoxib is 11.1 the solubility of the drug is likely to also be low at physiological pH.5 The oral bioavailability of celecoxib is between 22% and 40%.6 Thus, it is important to enhance the solubility and dissolution rate of celecoxib to improve its overall oral bioavailability.Celecoxib, a specific inhibitor of cycloxygenase-2 (COX-2) is a poorly water-soluble nonsteroidal antiinflammatory drug with relatively low bioavailability. The effect of ȕ-cyclodextrin on the aqueous solubility and dissolution rate of celecoxib was investigated. The possibility of molecular arrangement of inclusion complexes of celecoxib and ȕ-cyclodextrin were studied using molecular modeling and structural designing. The results offer a better correlation in terms of orientation of celecoxib inside the cyclodextrin cavity. Phase-solubility profile indicated that the solubility of celecoxib was significantly increased in the presence of ȕ-cyclodextrin and was classified as A L -type, indicating the 1:1 stoichiometric inclusion complexes. Solid complexes prepared by freeze drying, evaporation, and kneading methods were characterized using differential scanning calorimetry, powder x-ray diffractometry, and scanning electron microscopy. In vitro studies showed that the solubility and dissolution rate of celecoxib were significantly improved by complexation with ȕ-cyclodextrin with respect to the drug alone. In contrast, freeze-dried complexes showed higher dissolution rate than the other complexes.

CHARACTERISATION OF CATFISH (Clarias batrachus) OIL: β-CYCLODEXTRIN INCLUSION COMPLEX

“…The drastic change of the particles shape and aspects in the co-precipitation sample were indicative of the presence of a new solid phase, leading us to suggest the existence of a single phase. Previous study by Reddy et al [11] reported similar findings for a cyclodextrin: celecoxib system. Physical mixture of BCD with catfish oil (Figure 3 (d)) forms sticky and clumps to each other.…”

Improvement of Solubility and Antifungal Activity of a New Aminothiophene Derivative by Complexation with 2-Hydroxypropyl-β-cyclodextrin

“…These changes in the morphologic aspect of the complex samples suggest the existence of a single phase as previously related. 26,27 The comparison of these images suggests the formation of the complex between the 6CN10 and the HP-β-CD.…”

Preparation and Solid-State Characterization of Inclusion Complexes Formed Between Miconazole and Methyl-β-Cyclodextrin

“…DSC analysis has been shown to be a very powerful analytical tool in the characterization of solid-state interactions between drugs and CDs (25) and is a rapid analytical technique commonly used for evaluating drug-excipient interactions through the appearance, shift, or disappearance of endothermal or exothermal effects and/or variations in the relevant enthalpy values (26). The thermal curves of pure components and binary systems are shown in Fig.…”