Complexation of Zolpidem with 2‐Hydroxypropyl‐β‐, Methyl‐β‐, and 2‐Hydroxypropyl‐γ‐Cyclodextrin: Effect on Aqueous Solubility, Dissolution Rate, and Ataxic Activity in Rat

Trapani, Giuseppe; Latrofa, Andrea; Franco, Massimo; Pantaleo, Maria Rosaria; Sanna, Enrico; Massa, Federico; Tuveri, Francesca; Liso, Gaetano

doi:10.1002/1520-6017(200011)89:11<1443::aid-jps7>3.0.co;2-q

Cited by 37 publications

(21 citation statements)

References 17 publications

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“…Appreciable shift occurred in H (5) proton and H(3) proton in kneaded complexes KC1, KC2, KC4, which correlate the interaction of the drug and H(3)/H(5) protons of b-CD. Similar results were reported by many authors (11)(12).…”

Section: Nmrsupporting

confidence: 93%

Physicochemical characterization and in vitro dissolution behaviour of celecoxib-β-cyclodextrin inclusion complexes

Sinha¹,

Anitha²,

Ghosh³

et al. 2007

Acta Pharmaceutica

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Cyclodextrins are chemically and physically stable molecules formed by the enzymatic modification of starch (1). They are cyclomalto oligosaccharides composed of six, seven or eight a-D-glucopyranose units (a-, b-, g-CD, respectively). Their hollow structure enables them to host a variety of molecules (guests) partially or entirely in their hydrophobic caving. These inclusion complexes exist both in aqueous solution and in solid state. As a result of complexation of compounds by cyclodextrins, the apparent solubility of the molecule can be altered (2), stability of the compound in the presence of light and oxidizing conditions is increased (3) and volatility of compounds is decreased (4). Many scientists have studied the cyclodextrin complexes of various NSAIDs such as valdecoxib, diclofenac, piroxicam, ketoprofen, etc. and have showed their superiority over physical mixtures (5-8).Celecoxib, 4-[(5-(4-methyl phenyl)-3-trifluoro methyl)-1H-pyrazol-1-yl] benzene sulfonamide is a non steroidal anti-inflammatory drug that is a specific inhibitor of COX-2 enzyme. Celecoxib is widely used in the treatment of rheumatoid and osteoarthritis. According to the biopharmaceutical classification system, celecoxib belongs to class II type In this study, attempts were made to investigate the effects of b-cyclodextrin (b-CD) on the aqueous solubility and dissolution rate of celecoxib. Inclusion complexes were prepared by the kneading method and characterized by SEM, NMR, IR, DSC, and X-ray powder diffraction. Dissolution rate of the complexes was significantly greater than that of the corresponding physical mixtures and pure drug, indicating that the formation of inclusion complex increased the solubility of the poorly soluble drug celecoxib.

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Section: Nmrsupporting

confidence: 93%

Physicochemical characterization and in vitro dissolution behaviour of celecoxib-β-cyclodextrin inclusion complexes

Sinha¹,

Anitha²,

Ghosh³

et al. 2007

Acta Pharmaceutica

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“…The effect of complexation with ȕ-cyclodextrin on the solubility of celecoxib can be explained in terms of the reduction in the crystallinity of the drug caused by the freeze-drying process and the inclusion into the hydrophobic cavity of the ȕ-cyclodextrin. [22][23][24] The complexes prepared by kneading technique offer a dissolution rate of approximately 70% in 60-minutes, which may be of particular interest for industrial scale preparations because of the low cost and the simple process, which involves less energy, time, and equipment.…”

Section: Dissolution Rate Studiesmentioning

confidence: 99%

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

Reddy

Rehana

Sistla

et al. 2004

AAPS J

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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.

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“…The sequestration of a hydrophobic molecule or some part of it, inside the cavity usually alters the physicochemical properties of the encapsulated molecule, which is protected against the aqueous medium from light, oxidants or reactive attacks. CDs and their derivatives have received considerable attention in the pharmaceutical field [7][8][9][10][11] for the past few years due to their extensive use in drug delivery processes. In addition, they can be used to reduce or eliminate unpleasant smells or tastes, prevent drug-drug or drug-additive interactions.…”

Section: Introductionmentioning

confidence: 99%

Energetically favorable interactions between diclofenac sodium and cyclodextrin molecules in aqueous media

Mehta

Bhasin

Dham

2008

Journal of Colloid and Interface Science

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Complexation of Zolpidem with 2‐Hydroxypropyl‐β‐, Methyl‐β‐, and 2‐Hydroxypropyl‐γ‐Cyclodextrin: Effect on Aqueous Solubility, Dissolution Rate, and Ataxic Activity in Rat

Cited by 37 publications

References 17 publications

Physicochemical characterization and in vitro dissolution behaviour of celecoxib-β-cyclodextrin inclusion complexes

Physicochemical characterization and in vitro dissolution behaviour of celecoxib-β-cyclodextrin inclusion complexes

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

Energetically favorable interactions between diclofenac sodium and cyclodextrin molecules in aqueous media

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