Cyclodextrins In Aqueous Solution Research Articles

The application of co-melt-extruded poly(ε-caprolactone) as a controlled release drug delivery device when combined with novel bioactive drug candidates: Membrane permeation and Hanson dissolution studies

Eight bioactive drug compounds (abamectin, amoxicillin, dexamethasone, dexamethasone valerate, ketoprofen, melatonin, oestradiol 17β, and oestradiol benzoate) were combined via melt extrusion and disc pressing processes with a polycaprolactone (PCL) matrix and were then evaluated and compared via membrane diffusion and Hanson dissolution studies. This investigation was to determine the potential of this matrix to act as a controlled release drug delivery vehicle for a number of drugs not previously combined with PCL in a melt extrusion mix. The inclusion of the progesterone/PCL system, for which the drug release behaviour has been well studied before was intended for comparison with the PCL systems incorporating drugs that have received little research attention in the past. Initial studies centred on an evaluation of the permeation ability of the bioactive drugs dissolved in aqueous cyclodextrin solutions through a poly(ε-caprolactone) (PCL) membrane using Valia-Chien side-by-side cells. Permeation rates were mostly low and found to range from 0 to 122μgh−1 with only ketoprofen, melatonin, and progesterone displaying rates exceeding 20μgh−1. Hanson dissolution release profiles in aqueous alcohol were subsequently measured for the 9 melt extruded PCL/drug combinations and led to Hanson release rates of 0–556μgcm−2h−0.5 with dexamethasone, dexamethasone valerate, ketoprofen, melatonin, and progesterone giving values exceeding 100μgcm−2h−0.5. A number of drugs such as the dexamethasones probably performed better than they did in the permeability rate measurements because of the less polar aqueous alcoholic solvent used. In searching for useful correlations between the drug physicochemical properties and release rate, only a moderate correlation (R2=0.5675) between Hanson dissolution release rate and permeation rate was found. This suggests that the release rate and the permeation are both controlled by the rate of drug diffusion through the PCL with release rate involving an additional dissolution process (of the drug) before permeation occurs accounting for the moderate correlation. In general, of the eight drugs considered, it was clear that the oestradiol-based drugs, abamectin, and amoxicillin were generally not suited to drug delivery via PCL under the conditions used. However, ketoprofen was found to be very suitable as a drug candidate for melt extrusion with PCL with dexamethasone valerate, dexamethasone, and melatonin also showing potential as candidates though to a much lesser extent.

Gas–liquid partitioning of halogenated volatile organic compounds in aqueous cyclodextrin solutions

Gas–liquid partitioning coefficients ( K GL) were measured for halogenated volatile organic compounds (VOCs), namely 1-chlorobutane, methoxyflurane, pentafluoropropan-1-ol, heptafluorobutan-1-ol, α, α, α-trifluorotoluene, and toluene in aqueous solutions of natural α-, β-, and γ-cyclodextrins (CDs) at temperatures from (273.35 to 326.35) K employing the techniques of headspace gas chromatography and inert gas stripping. The binding constants of the 1:1 inclusion complex formation between the VOCs and CDs were evaluated from the depression of the VOCs volatility as a function of CD concentration. The host–guest size matching and the hydrophobic interaction concept were used to rationalize the observed widely different affinity of the VOC–CD pairs to form the inclusion complex. The enthalpic and entropic component of the standard Gibbs free energy of complex formation as derived from the temperature dependence of the binding constant indicate the thermodynamic origin of the binding to vary greatly among the systems studied, but follow the global enthalpy–entropy compensation relationships reported previously in the literature.

Complexation of Microcystins and Nodularin by Cyclodextrins in Aqueous Solution, a Potential Removal Strategy

Cyanotoxins are potent toxic compounds produced by cyanobacteria during algal blooms, which threaten drinking water supplies. These compounds can poison and kill animals and humans. The host-guest interactions of α-, β-, and γ-cyclodextrins (CD) with problematic cyanotoxins, including microcystins (MCs) and nodularin (NOD), were investigated to demonstrate the potential application of CDs for the removal of these toxins from drinking water or applications related to their separation or purification. MCs and NOD have a hydrophobic Adda chain, which contains diene and benzene functional groups. The complexation of these cyanotoxins with CDs was monitored by nuclear magnetic resonance (NMR). The (1)H NMR spectra for MCs are unchanged upon addition of α-CD (smallest host). However, addition of larger hosts, β-CD and γ-CD, leads to significant changes in chemical shifts of the benzene and diene resonances on the 3-amino-9-methoxy-2,6,8-trimethal-10-phenyldeca-4,6-dienoic acid (Adda) chain of MCs and NOD. Solution pH, natural organic matter, and salinity do not appreciably influence the host-guest complexation under our experimental conditions. The experimental binding constants for MCs and NOD with γ-CD are relatively strong, ranging from 1155 to 507 M(-1). The observed changes in chemical shifts for specific protons and competitive binding experiments demonstrate a 1:1 inclusion complex between γ-CD and MCs or NOD, with the Adda chains threading through the CD ring, resulting in an inclusion complex. Our results suggest that CD-type substrates are useful hosts for the complexation of MCs and NOD. CDs can be readily attached to a number of polymeric or solid supports and their functionality tailored to strengthen specific host-guest interactions. With further development of such materials, CD host-guest chemistry may find direct application in the removal and/or separation science of these compounds.

Comparison between 2-hydroxypropyl-β-cyclodextrin and 2-hydroxypropyl-γ-cyclodextrin for inclusion complex formation with danazol

Complexation in solution between danazol and two different cyclodextrins [2-hydroxypropyl-β-cyclodextrin (HP-β-CD) and 2-hydroxypropyl-γ-cyclodextrin (HP-γ-CD)] was studied using phase solubility analysis, and one- and two-dimensional 1H-NMR. The increase of danazol solubility in the aqueous cyclodextrin solutions showed a linear relationship (AL profile). The apparent stability constant, K1:1, of each complex was calculated and found to be 51.7 × 103 and 7.3 × 103 M−1 for danazol–HP-β-CD and danazol–HP-γ-CD, respectively. 1H-NMR spectroscopic analysis of varying ratios of danazol and the different cyclodextrins in a mixture of EtOD–D2O confirmed the 1:1 stoichiometry. Cross-peaks, from 2D ROESY 1H-NMR spectra, between protons of danazol and H3′ and H5′of cyclodextrins, which stay inside the cyclodextrin cavity, proved the formation of an inclusion complex between danazol and the cyclodextrins. For HP-β-CD, the inclusion complex is formed by entrance of the isooxazole and the A rings of danazol in the cyclodextrin cavity. For HP-γ-CD, two different inclusion structures may exist simultaneously in solution: one with the isooxazole and A ring in the cavity and the other with the C and D ring inside the cavity. DLS showed that self-aggregation of the CD’s was absent in the danazol HP-β-CD system up to a CD concentration of 10% and in the danazol HP-γ-CD system up to a CD concentration of 5%.

Stability and Structure of Inclusion Complexes of Zaleplon with Natural and Modified Cyclodextrins

The interaction between zaleplon (ZAL) and different cyclodextrins in aqueous solutions was investigated by spectrofluorimetric and phase solubility studies. Stability constants determined by both methods showed that among natural cyclodextrins, β-cyclodextrin (βCD) formed the most stabile complex but its solubilizing efficiency was limited. Among βCD derivatives, the complex stability and solubilisa- tion efficiency decreased in order: randomly methylated-βCD (RAMEB) > sulphobutylether-βCD (SBEβCD ) > hydroxypropyl-βCD (HPβCD). The inclusion complexes of ZAL with βCD and RAMEB were further characterised by 1 H-NMR spectroscopy and the inclusion complex formation was confirmed in both cases. ROESY spectra showed two binding modes between ZAL and βCD which exist simulta- neously in the solution. The first binding mode occurs by the inclusion of the phenyl ring of ZAL into the βCD central cavity via the wider rim of the cyclodextrin cone and is dominant. The second one is formed by the inclusion of pyrazolo(1,5-a)pyrimidine ring of ZAL.(doi: 10.5562/cca1800)

Unique Organogel Formation with Macroporous Materials Constructed by the Freeze−Drying of Aqueous Cyclodextrin Solutions

Macroporous cyclodextrin materials (MP-alpha-, beta-, and gamma-CDs) were easily fabricated by the freeze-drying of aqueous solutions of alpha-, beta-, and gamma-CDs. These MP-CDs showed the absorption ability toward various organic solvents and oils to give organogels at ambient temperature. The morphological changes of the MP-CD microstructures were observed through the absorption of organic solvents. In particular, the absorption of polar organic solvents with hydrogen-bond forming ability, including 1,4-dioxane and ethanol, by the MP-CDs caused remarkable morphological changes in the microstructures. The absorption of these polar solvents by MP-alpha- and gamma-CDs resulted in the formation of channel-type assemblies of alpha- and gamma-CDs, respectively.

NMR diffusometry applied to liquids

Gradient based nuclear magnetic resonance spectroscopy provides a convenient method to determine self-diffusion coefficients especially in liquid samples. The method has many advantages including short experiment time, sensitivity, molecular resolution, and accuracy — all without the need for adding perturbing probes or chemically introducing isotopes. In this contribution we introduce the method and discuss through several examples its uses. We discuss how the method provides diffusion coefficients in supercooled water and alcohol–water mixtures. In ionic liquids the method conveys information about single ion mobilities and cluster formation. In self-assembling systems possible aggregate growth can be conveniently investigated. We demonstrate, based on self-diffusion coefficients, that there is little evidence for aggregation in aqueous solutions of cyclodextrins. Finally, we demonstrate how NMR diffusometry can be used to determine the diffusion of water inside a biological cell. It goes without saying that such data are very important in the understanding of transport properties in cells, where diffusion plays a major role.

Effect of self-aggregation of γ-cyclodextrin on drug solubilization

The purpose of this study was to investigate the physicochemical properties of drug-saturated aqueous cyclodextrin (CD) solutions. Phase solubility profiles of different drugs were determined in aqueous solutions containing γ-cyclodextrin (γCD) and/or hydroxypropyl-γ-cyclodextrin (HPγCD) in absence or presence of water-soluble polymers. 1H-NMR and turbidity analysis were performed as well as permeation studies. Phase solubility diagrams showed that the observed γCD content (1–20% w/v) was only slightly different from the theoretical values for aqueous solutions that had been saturated with indomethacin, diclofenac sodium or amphotericin B, all displayed A-type profiles, while it was less than the theoretical value in solutions that had been saturated with corticosteroids (hydrocortisone and dexamethasone) that displayed BS-type profiles. In the latter case self-assemble of drug/CD complexes decreased the overall CD solubility. Water-soluble polymers enhanced aqueous solubility of the drugs tested by stabilizing the drug/CD complexes, i.e. enhancing their stability constants, without affecting the observed aqueous γCD solubility. When the drug solubility leveled off (the BS-type profiles) the amount of dissolved γCD increased and approached the theoretical values. Hydrocortisone formed partial inclusion complex with γCD and HPγCD and no non-inclusion or aggregates could be detected in diluted solutions by 1H-NMR. Both permeation and turbidity studies showed that formation of dexamethasone/γCD complex promoted CD aggregation. All these observations indicate that CD aggregate formations play a role in CD solubilization of lipophilic and poorly water-soluble drugs and that the water-soluble polymers enhance the complexation efficiency of γCD and HPγCD by stabilizing the self-assembled drug/CD nanoparticles and promote non-inclusion complex formation.

Interactions of xanthine and its derivatives with cyclodextrins in aqueous solutions

Using calorimetry, 1H NMR, UV spectroscopy, and solubility methods, the interactions of natural and hydroxypropylated 6h-, β-, and γ-cyclodextrins with xanthine and its methylated derivatives (theophylline, theobromine, and caffeine) were studied in aqueous solutions at 298.15 K. Cyclodextrins revealed low complexation ability toward xanthine and its methylated derivatives. Hydroxypropyl-γ-cyclodextrin with the largest internal cavity is the most effective solubilizing agent for this type of compounds. The calculated thermodynamic parameters are discussed in terms of structural effects of cyclodextrins and purine alkaloids on the character of their intermolecular interactions in aqueous medium.

Cyclodextrins as solubilizers: Formation of complex aggregates

Three different techniques were applied to investigate aggregation of drug/cyclodextrin complexes, that is, drug permeation through semi-permeable membranes, determination of changes in the value of activity coefficients of drug/cyclodextrin complex solutions and transmission electron microscopy (TEM). The aqueous solutions studied contained γ-cyclodextrin, 2-hydroxypropyl-γ-cyclodextrin or mixtures thereof, and hydrocortisone, amphotericin B, diclofenac sodium or indomethacin. The permeation studies indicated that drug/cyclodextrin complex monomers (i.e., unaggregated complexes) were dominating at cyclodextrin concentrations below 5% (w/v). Then formation of aggregates gradually increased with increasing cyclodextrin concentration until all increase in dissolved drug/cyclodextrin complexes was due to formation of cyclodextrin aggregates. This happened even though the observed phase-solubility diagrams were linear, that is, were of AL-type. The activity coefficients showed positive deviation from ideal state. This positive deviation is due to concurrent of several processes, that is, hydration, aggregation and complex formation. The observed deviations from ideality indicated that complex aggregates were formed in the aqueous complexation media. TEM pictures showed formation of aggregates in both pure aqueous cyclodextrin solutions as well as in cyclodextrin solutions that had been saturated with hydrocortisone. The aggregate diameter was between 10 and 100 nm but larger aggregates with diameter of about 200 nm were formed through assemble of smaller aggregates. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:719–729, 2010

The Pseudophase Approach to Assessing Chemical Partitioning in Air−Water−Cyclodextrin Systems

Henry's Law constants (HLCs) of several common, subsurface hydrophobic organic pollutants (HOPs) including trichloroethylene (TCE), perchloroethylene (PCE) and benzene, toluene, ethylbenzene, and o-xylene (BTEX), were measured using a static headspace phase ratio (SHPR) method over a range of temperatures (35, 45, 55, and 65 degrees C) and experimentally and operationally relevant cyclodextrin (CD) concentrations (0, 10, 20, 50, and 100 g L(-1)). In aqueous CD solutions, HLC values decrease according to a power law relationship with increasing CD concentration due to an apparent solubility enhancement caused by HOP partitioning to the hydrophobic cavity of CD molecules. The temperature dependence of air-water partitioning under the influence of CD was well described by the van't Hoff equation for all HOPs tested. A three-phase equilibrium model was used to interpret air-water-CD partitioning data, treating CD as a pseudophase. Our results show that HOP CD-water partition coefficients decrease linearly with increasing temperature. CD-water partition coefficients were generally independent of CD concentration, with a few exceptions. Comparison of our results for hydroxypropyl-beta-CD and TCE to those from another study showed several major discrepancies, which were attributed to differences in the experimental methods employed. Our attempt to correlate CD-water partition coefficients with HOP chemical properties indicates that correlations based on individual chemical descriptors (e.g., aqueous solubility, octanol-water partition coefficient, molecular volume or ET (30) polarity index) will not be sufficient to obtain accurate estimates of HOP CD-water partition coefficients for other compounds with differing chemical structures.

PAH contaminated soil remediation by reusing an aqueous solution of cyclodextrins

We studied the possibility to re-use an aqueous solution of methyl-β-cyclodextrin (bpmCD) in order to decontaminate a soil polluted by phenanthrene and pyrene. The loss of bpmCD in the soil was insignificant. In order to eliminate polycylic aromatic hydrocarbons (PAHs) from the contaminated aqueous solution, on one hand we tested their photodegradation using TiO 2 suspensions. But it was inefficient, because of the stabilisation of PAHs within the cavity of bpmCD. On the other hand, we removed PAHs by liquid-liquid extraction with colza oil. This allowed the regeneration of cyclodextrins, by concentrating the pollutants in the organic phase with a small loss of carrier. Contaminated soils were almost completely de-polluted after 2 d of re-circulation, using a 10 mM solution of bpmCD. To reduce the amount of bpmCD loss in the oil phase, we set the fraction of colza oil low, by using a micro-emulsion or by impregnating an organic membrane with the oil. We found this last possibility more interesting.

Characterization and in vitro evaluation of the formoterol/cyclodextrin complex for pulmonary administration by nebulization

The aim of this work is to investigate the effect of cyclodextrin complexation on the pulmonary deposition of formoterol, a drug with a very poor aqueous solubility, after jet nebulization. Two types of cyclodextrins, a hydroxypropyl β cyclodextrin (Kleptose HP) and a polydispersed methyl β cyclodextrin (Crysmeb) were used. The interactions of formoterol with the cyclodextrins were studied by NMR. The aqueous cyclodextrin solutions containing formoterol were defined by their physicochemical properties in relation to nebulization capacity: density, surface tension and viscosity. Nebulization efficiency was evaluated by measuring droplet size, nebulization rate, quantity nebulized and nebulization time. The NMR ROESY spectra suggest that formoterol or a part of it is included inside the cyclodextrins. Densities and viscosities of the solutions tested are close to those of water; the lower surface tensions compared to water (53.7 and 56.7 vs 70 mN/m) favour the formation of small droplets. The aqueous solutions of cyclodextrins and formoterol studied can generate aerosols with a particle size that is compatible with pulmonary deposition. Respirable fraction values between 57.5% and 88 % were obtained when nebulizing the solutions with four nebulizers that differ geometrically. Nebulization rates varied from 0.19 to 0.47 g/min. Large quantities of drug nebulized over acceptable delivery times were observed. β-cyclodextrin derivatives can be used to formulate nebulizable solutions of formoterol. It is indispensable to define the appropriate nebulizers and operating conditions associated with the solutions to obtain adapted and reproducible activity.

New insight into the discrimination between omeprazole enantiomers by cyclodextrins in aqueous solution

We report results regarding the use of 1H-NMR spectroscopy in the study of the conformational behaviour and optical activity of omeprazole. Changes in the chemical shifts of chosen atoms reveal that the conformational behaviour of omeprazole is temperature and pH sensitive. Separation and identification of omeprazole enantiomers in the presence of natural and derivative cyclodextrins, such as β-cyclodextrin (βCD) and methyl-β-cyclodextrin (MβCD) are achieved using 1H-NMR spectroscopy, with information from molecular dynamics simulation. This work shows that βCD includes preferentially R-(–)-omeprazole, acting as a chiral selector. This discrimination of omeprazole enantiomers by cyclodextrins allows development of pharmaceutical formulations with a better bioavailability profile.

Complexation of niflumic acid with native and hydroxypropylated α‐ and β‐cyclodextrins in aqueous solution

AbstractInteractions between niflumic acid and native and hydroxypropylated α‐ and β‐cyclodextrins (CDs) were investigated by 1H NMR, UV‐vis spectroscopy, densimetry, and calorimetry at pH = 7.4 (phosphate buffer) and T = 298.15 K. Thermodynamic parameters of 1:1 complex formation were calculated and discussed in terms of influence of cavity size and availability of hydroxypropyl substituents on the complex stability. The 1H NMR data indicated the inclusion of niflumic acid into macrocyclic cavity of all CDs under study. It was found that both phenyl and pyridine rings of niflumic acid molecule can be included in the cyclodextrin cavity. The co‐existence of two different kinds of 1:1 inclusion complexes in the solution was suggested. In spite of the fact that binding of niflumic acid with α‐cyclodextrin is more enthalpically favorable, stability of the inclusion complexes is very low due to the enthalpy–entropy compensation effect. Complex formation of β‐CDs with niflumic acid is characterized by the higher enthalpy and entropy changes caused by more intense dehydration. Introduction of hydroxypropyl groups in the cyclodextrin molecule was found to promote the binding with niflumic acid. Copyright © 2008 John Wiley & Sons, Ltd.

Use of Water Spin−Spin Relaxation Rate to Probe the Solvation of Cyclodextrins in Aqueous Solutions

1H spin-spin relaxation rate constant, R2, of water was measured by using the Carr-Purcell-Meiboom-Gill sequence in aqueous solutions of native cyclodextrins (alpha, beta, and gamma-CD) and chemically modified CDs in order to probe the structuring of the water surrounding these cyclic carbohydrate molecules. R2 values for water in solutions containing glucose and dextran were also measured for comparison. A two-site model for bonded and free water molecules was used to fit the results for the dependence of R2 on the solute concentrations. The order of relaxation rates for water in aqueous solution at a fixed specific hydroxyl group concentration is glucose>dextran congruent with CDs. No significant difference was observed for R2 of water in solutions containing native CDs, which indicates that the size and nature of the cavity has a small effect on the spin-spin relaxation times of water. The lower relaxation rate for water in CD solutions was attributed to the intramolecular hydrogen bonding formed between the secondary hydroxyl groups that line the rim of the CDs. For comparison, the relaxation rates for water in solutions of two chemically modified CDs were also studied.

Hydration and Dynamic Behavior of Cyclodextrins in Aqueous Solution

The hydration state and dynamics of plain and chemically modified cyclodextrins (CDs) in aqueous solution were investigated by using dielectric relaxation measurements at 25 degrees C over a wide frequency range up to 20 GHz, which is the relaxation frequency of pure liquid water molecules. The obtained dielectric relaxation spectra were decomposed into two major and one minor relaxation modes with relaxation times of approximately 8.3, 20-25, and 1000-2500 ps, respectively, depending on the CD species. The two major modes, fast and medium, were attributed to a rotational relaxation process of water molecules belonging to the bulk (free) state and an exchange of water molecules hydrated to CDs owing to hydrogen bond formation. The hydration numbers of the CDs strongly depend on the number of hydroxy (OH) groups controlled by chemical modification such as methylation. Increasing the number of methoxy or 2-hydroxypropoxy groups increases the hydration number of CD molecules, and results in higher solubilities of the chemically modified CDs than those of the plain CDs. The minor, slow mode was assigned to overall rotational relaxation for CDs with finite permanent dipole moments, which also depends on the number of OH groups.

Inclusion of menadione with cyclodextrins studied by calorimetry and spectroscopic methods

AbstractComplex formation of menadione with α‐, hydroxypropyl α‐, β‐, hydroxypropyl‐β‐, methyl‐β‐ and hydroxypropyl‐γ cyclodextrins in aqueous solution at 298.15 K was studied by using isothermal titration calorimetry, 1H NMR, and UV–vis spectrophotometry. The experimental data indicated the partial insertion of menadione into macrocyclic cavity upon formation of two alternative types of 1:1 inclusion complexes, whose thermodynamic parameters (K, ΔcG0, ΔcH0, and ΔcS0) were calculated. The influence of host size on the complex formation process was analyzed. β‐Cyclodextrin and its hydroxypropylated and methylated derivatives were found more effective binders towards menadione than α‐ and γ‐cyclodextrins. Copyright © 2007 John Wiley & Sons, Ltd.

Fluorescence enhancement of the aflatoxin B 1 by forming inclusion complexes with some cyclodextrins and molecular modeling study

The interaction between the aflatoxin B 1 (AFB 1) and three cyclodextrins, α-cyclodextrin ( α-CD), β-cyclodextrin ( β-CD) and heptakis-2,6-dimethyl- o- β-cyclodextrin (ome-CD), was studied by spectrofluorescence technique. It was found that the inclusion association behavior occurs for the complexes of cyclodextrins with AFB 1. The fluorescence of AFB 1 is generally enhanced in the complexes with cyclodextrins in aqueous solutions. The inclusion complex constants of the three types of cyclodextrins at different temperatures were evaluated from Benesi–Hildebrand plot and also by non-linear regression analysis. These cyclodextrins can only form the 1:1 (host:guest) inclusion complex in the studied temperature range of 20–50 °C. The enthalpy (Δ H°) and entropy (Δ S°) changes of complexation were extracted from the temperature dependency of complex formation constants ( K). Temperature-dependent measurements showed that the association step is controlled by enthalpy–entropy compensation effect. The use of ome-CD generally resulted in the greatest fluorescence intensity. On the other hand, the discrepancy between the exhibited enhanced fluorescence and thermodynamic parameters (Δ G°) is proposed to be different only by the orientation of the AFB 1 within the cyclodextrin cavity. To find the most favorable structure, the geometry of complex was investigated by molecular modeling approach employing the semiemperical HF–SCF calculations.

Changes in the reactivity of the fluorescent reagents carbazole-9-carbonyl chloride and 9-carbazolylacetic acid in the presence of cyclodextrins

Carbazole-9-carbonyl chloride (C9CC) and 9-carbazolylacetic acid (9CAA) were selected as model fluorescent reagents. The effect of different chemically modified cyclodextrins (CDs) added to the aqueous solutions of these reagents was studied in water and in buffered aqueous solutions at pH 4.5 and 8.8. The CDs employed were 2-hydroxypropyl-β-cyclodextrin (HP-βCD), 2,3-di-O-methyl-β-cyclodextrin (DM-βCD) and 2,3,6-tri-O-methyl-β-cyclodextrin (TM-βCD). The inclusion of these reagents inside the cavities of the CDs was verified and this process can affect the derivatization reaction because CDs can modify the reactivity of the guest molecules. The basic conditions necessary for the derivatization reaction between C9CC and amines lead to the formation of carbazole anion through hydrolysis followed by decarboxylation. In the presence of CDs, the hydrolysis-decarboxylation of carbazole-9-carbonyl chloride is faster than in buffered aqueous homogeneous solutions. The behaviour observed for these reagents in aqueous solutions of CDs was compared to the one observed in basic ethanolic solutions. These changes are particularly noticeable in the case of 2,3-di-O-methyl-β-CD and 2-hydroxypropyl-β-CD. The characteristics of the fluorescent reagents are compared to carbazole and 9-methylcarbazole as model compounds.