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PubMedDate not supplied

Characterization of interacting ferrocene-cyclodextrin systems and their role in mediated biosensors.

Inclusion complexes of 1,1'-dimethylferrocene (DMFe) with alpha-, 2-hydroxypropyl-beta- or gamma-cyclodextrins were formed in aqueous systems. For the first time, the interacting DMFe-cyclodextrin systems have been characterized using cyclic voltammetry which enabled the estimation of the complexation order, the formation constant and the diffusivity. Cyclic voltammetry was performed at a stationary electrode, yielding complexation ratios of 1:2 for DMFe with alpha-cyclodextrin and 1:1 with the other two cyclodextrins, as expected from the known cavity dimensions for the cyclodextrins. Formation constants of 4.4 x 10(4) M-2, 1.2 x 10(3) M-1 and 2.9 x 10(2) M-1 were then determined for the complexes between DMFe and the alpha-, beta- and gamma-cyclodextrins, respectively, in relative agreement with the literature. The maximum complexation efficiency, diffusivity and solubility were observed for the DMFe:2-hydroxypropyl-beta-cyclodextrin inclusion complex, which, combined with cost factors, resulted in the selection of this form for bioelectrocatalysis studies. The efficiency of the complex as a mediator for the glucose:glucose oxidase system was determined by measuring the rate constant (ks) for reaction of the oxidized DMFe with the reduced enzyme. The ks value decreased from 3.4 x 10(4) M-1 s-1 to 1.9 x 10(4) M-1 s-1 with an increase in 2-hydroxypropyl-beta-cyclodextrin concentration from 4 mM to 10 mM. In this range, the ks value is similar to that of free ferrocene, implying a high efficiency of the DMFe:2-hydroxypropyl-beta-cyclodextrin inclusion complex.

Biosensing Techniques↗
PubMed2002

Topical formulation studies with DEET (N,N-diethyl-3-methylbenzamide) and cyclodextrins.

The purpose of this study was to investigate the utility of cyclodextrins as a safer alternative to the commonly used cosolvent ethanol in topical N,N-diethyl-3-methylbenzamide (DEET) formulations. Ethanol is a known penetration enhancer and would ideally not be used in a formulation containing DEET, a compound known for its potential toxicity. DEET formulations were prepared containing up to 20% w/w gamma-cyclodextrin (GCD) or 30% w/w hydroxypropyl-beta-cyclodextrin (HPBCD). These formulations were evaluated by determining the release rate of DEET from its vehicle through a synthetic membrane into a receiver medium with a high affinity for DEET using a fully automated Franz-diffusion cell system. DEET release was measured by ultraviolet spectrophotometry at 260 nm. Both the traditional Higuchi release model and an alternate repeated measures analysis of variance with nested factors were used to analyze the data. The influence of the cyclodextrins on the volatility of DEET was determined by solid-phase microextraction. Morphological characterization of the formulations was performed by light microscopy. Physical stability of the formulations was evaluated by rheology in an accelerated study performed at 50 degrees C for 28 days. The cyclodextrins caused a decrease in the release of DEET from its vehicle compared with an ethanol-containing formulation. This effect became more pronounced as the amount of cyclodextrin in the formulation was increased. The addition of the cyclodextrins resulted in a cream-like product compared with the ethanol formulation, which was a lotion. The DEET formulations had the following rank order of volatility: ethanol < DEET = GCD < HPBCD. Examination of the formulations by light microscopy indicated that the CD-based formulations produced a smaller and more homogeneous droplet size distribution than the ethanol-based formulations. The accelerated physical stability study indicated that cyclodextrin-based formulations are both technically and commercially feasible. Cyclodextrins are a promising alternative to ethanol in DEET-containing formulations. The reduced release rate of DEET from these formulations suggests that the toxic potential of DEET may be decreased in these products, while its repellency and stability are maintained.

Administration, Topical↗
PubMed1995

Population characteristics of cyclodextrin complex stabilities in aqueous solution.

Binding constants (K11) of 1:1 complexes of alpha-cyclodextrin, beta-cyclodextrin, and gamma-cyclodextrin with many substrates (guests) were collected from published sources and subjected to statistical analysis. All systems refer to 25 +/- 5 degrees C and aqueous solution. The frequency distributions of log K11 are satisfactorily described by normal distributions with the following parameters (n = number of complexes, mu = population mean, sigma = population standard deviation): alpha-cyclodextrin, n = 663, mu = 2.11, sigma = 0.90; beta-cyclodextrin, n = 721, mu = 2.69, sigma = 0.89; gamma-cyclodextrin, n = 166, mu = 2.55, sigma = 0.93. Stabilities of pairs of cyclodextrin complexes with a common substrate are not precisely correlated, but they do not appear to be wholly independent quantities. The stabilities of alpha-cyclodextrin complexes are consistent with a recent interpretation of solvent effects on alpha-cyclodextrin complex stabilities.

Cyclodextrins↗
PubMed1988

Effect of cyclodextrins on anthracycline stability in acidic aqueous media.

The effect of cyclodextrins on the stability of six anthracyclines in acidic medium at 50 degrees C has been investigated using a stability-indicating high pressure liquid chromatographic method. The influences of various parameters, such as the structure of cyclodextrins (alpha-cyclodextrin, beta-cyclodextrin, dimethyl-beta-cyclodextrin and gamma-cyclodextrin) and anthracyclines, cyclodextrin concentration, the pH and the presence of a co-solvent, are investigated. Lineweaver-Burk plots were used to calculate the stability constants of the various inclusion complexes as well as the rate constants for degradation of the anthracycline guest molecules in the complexes with the host cyclodextrins. Anthracyclines complexate only with gamma-cyclodextrin to a substantial extent. On complexation the stability of the guest molecule increases, however, the degradation pattern does not alter. The influence of the pH on the degradation of the included molecule is identical to that of the free drug. Addition of co-solvents, such as acetonitrile, causes decomposition of the complex.

Antibiotics, Antineoplastic↗
PubMed2001

A comparison of phosphated and sulfated beta-cyclodextrins as chiral selectors for capillary electrophoresis.

The enantioseparation capabilities of three different functionalized beta-cyclodextrins, two sulfated beta-cyclodextrins with 4 and 15 nominal degrees of substitution and a phosphated beta-cyclodextrin with 8 degrees of substitution, were compared. While anodic detection was used with both sulfated cyclodextrins, the phosphated cyclodextrin required cathodic detection suggesting either lower ionization of the phosphated cyclodextrin or generally lower affinity of the analytes for the phosphated cyclodextrin. The effects of several experimental parameters were evaluated with respect to enantioseparation. The degrees of substitution of the cyclodextrin, pH of the background electrolyte as well as the concentration of the functionalized beta-cyclodextrin, each had a significant influence on the successful enantiomeric separation of the chiral drugs investigated.

Cyclodextrins↗
PubMed2006

Interaction of omeprazole with a methylated derivative of beta-cyclodextrin: phase solubility, NMR spectroscopy and molecular simulation.

PURPOSE: Cyclodextrins are known to be good solubility enhancers for several drugs, improving bioavailability when incorporated in pharmaceutical formulations. In this work we intend to assess and characterize the formation of inclusion complexes between omeprazole (OME) and a methylated derivative of beta-cyclodextrin, methyl-beta-cyclodextrin (MbetaCD). A comparison with results obtained from the most commonly used natural cyclodextrin, beta-cyclodextrin (betaCD) is also presented in most cases. MATERIALS AND METHODS: The interaction of OME with the mentioned cyclodextrins in aqueous solutions was studied by phase solubility studies, 1D (1)H and 2D rotating frame nuclear overhauser effect NMR spectroscopy (ROESY) and Molecular Dynamics. RESULTS: The solubility of OME was significantly increased by formation of inclusion complexes with each cyclodextrin. Phase solubility studies and continuous variation plots revealed that OME forms an inclusion complex in a stoichiometry of 1:1 with both cyclodextrins. (1)H NMR and ROESY spectra of the inclusion complexes indicated that the benzimidazole moiety is included within the cyclodextrins cavities. Molecular dynamics showed that OME is more deeply included in the MbetaCD than in betaCD cavity, in agreement with a larger apparent stability constant (K (S)) obtained for the inclusion complex with MbetaCD. CONCLUSIONS: MbetaCD proved to be an efficient enhancer of OME solubility, thus possessing characteristics for being an useful excipient in pharmaceutical formulations of this drug.

Chemical Phenomena↗
PubMed2005

Effect of SBE7-beta-cyclodextrin complexation on carbamazepine release from sustained release beads.

The effect of SBE7-beta-cyclodextrin together with hydroxypropylmethyl cellulose (HPMC) or polyvinylpyrrolidone (PVP) on the saturated solubility and delivery of carbamazepine (a poorly soluble drug) from sustained release (SR) beads was investigated. Carbamazepine solubility at room temperature increased from 0.1 to 5.4mg/ml by forming an inclusion complex with SBE7-beta-cyclodextrin (15%w/v). HPMC (0.1%w/v) also increased the aqueous solubility of carbamazepine, acting both alone and synergistically with SBE7-beta-cyclodextrin, to produce solubility values of 0.26 and 8.1mg/ml respectively. PVP (0.1-0.5%w/v) had no effect on carbamazepine solubility, either alone or in combination with SBE7-beta-cyclodextrin. The addition of SBE7-beta-cyclodextrin to SR beads increased the rate of carbamazepine release. In addition, comparable release rates where obtained when lower ratios of SBE7-beta-cyclodextrin together HPMC were incorporated in the SR bead. Therefore this ternary drug cyclodextrin polymer system was considered preferable over the binary drug cyclodextrin system for SR beads, as less cyclodextrin was required. However, both binary and ternary approaches were considered suitable techniques to improve the release rate and potentially the in vivo bioavailability of poorly soluble drugs that had previously exhibited slow or incomplete release from SR beads.

Algorithms↗
PubMed2002

Synthesis and characterization of water-soluble hydroxybutenyl cyclomaltooligosaccharides (cyclodextrins).

We have examined the synthesis of hydroxybutenyl cyclomaltooligosaccharides (cyclodextrins) and the ability of these cyclodextrin ethers to form guest-host complexes with guest molecules. The hydroxybutenyl cyclodextrin ethers were prepared by a base-catalyzed reaction of 3,4-epoxy-1-butene with the parent cyclodextrins in an aqueous medium. Reaction byproducts were removed by nanofiltration before the hydroxybutenyl cyclodextrins were isolated by co-evaporation of water-EtOH. Hydroxybutenyl cyclodextrins containing no unsubstituted parent cyclodextrin typically have a degree of substitution of 2-4 and a molar substitution of 4-7. These hydroxybutenyl cyclodextrins are randomly substituted, amorphous solids. The hydroxybutenyl cyclodextrin ethers were found to be highly water soluble. Complexes of HBen-beta-CD with glibenclamide and ibuprofen were prepared and isolated. In both cases, the guest content of the complexes was large, and a significant increase in the solubility of the free drug was observed. Dissolution of the complexes in pH 1.4 water was very rapid, and significant increases in the solubility of the free drugs were observed. Significantly, after reaching equilibrium concentration, a decrease in the drug concentration over time was not observed.

Butanols↗
PubMed1999

Influence of the preparation method on the physicochemical properties of ketoprofen-cyclodextrin binary systems.

Binary systems of ketoprofen with native crystalline beta-cyclodextrin and amorphous statistically substituted methyl-beta-cyclodextrin were investigated for both solid phase characterization (Differential Scanning Calorimetry, powder X-ray diffraction, Infrared Spectroscopy, Scanning Electron Microscopy) and dissolution properties (dispersed amount and rotating disc methods). Grinding, kneading, sealed-heating and colyophilization of equimolar combinations of ketoprofen with methyl-beta-cyclodextrin, as well as colyophilization of analogous combinations with beta-cyclodextrin, led to amorphous products. Crystalline drug, instead, was still clearly detectable in coground, kneaded and sealed-heated products with beta-cyclodextrin. Both the preparation method, and even more the nature of the carrier, played an important role in the performance of the system. Colyophilized and sealed-heated products showed the best dissolution properties. However, independently of the preparation technique, all combinations with methyl-beta-cyclodextrin yield better performances than the corresponding ones with the beta-cyclodextrin. Moreover, intrinsic dissolution rate of ketoprofen from simple physical mixture with the beta-cyclodextrin derivative was even five-fold higher than that from the best product with the parent beta-cyclodextrin.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2003

Changing mechanisms in the beta-cyclodextrin-mediated hydrolysis of phenyl esters of perfluoroalkanoic acids.

The rate of hydrolysis of esters CF(3)(CF(2))(n)COOPh (1 (n = 1), 2 (n = 2), and 3 (n = 6)) was measured at pH 6.00 and at pH higher than 9.00 in the presence of beta-cyclodextrin (beta-CD). For compounds 1 and 2 the reaction rate decreases as the beta-CD concentration increases, and they show saturation effects at all pH. It is suggested that the substrate forms an inclusion complex with cyclodextrin. Analysis of the rate data allows calculation of the association equilibrium constant, K(CD), the rate constant for the reaction of the included compound, k(c), and K(TS) which is the hypothetical association equilibrium constant for the transition state of the cyclodextrin-mediated reaction. The dependence of log K(CD) and log K(TS) with the number of atoms in the chain is different. We suggest that the reactions of 1 and 2 take place with the perfluorinated alkyl chain included in the cavity, whereas the transition state for the reaction of phenyl trifluoroacetate involves a complex with the aryl ring inside the cavity. At low pH the inhibition comes from the protection of the carbonyl group toward nucleophilic attack by water. In basic pH the reaction of HO(-) as an external nucleophile is also inhibited. The cyclodextrin-mediated reaction involves the ionized OH group at the rim of the cyclodextrin cavity with poor efficiency due to an unfavorable orientation of the substrate in the complex. On the other hand, the reaction of compound 3 is strongly accelerated by cyclodextrin because the association of the substrate with cyclodextrin competes with the monomer-aggregate equilibrium and at high enough cyclodextrin concentration the main species present in solution is the complex between 3 and cyclodextrin.

Algorithms↗
PubMed2004

Cyclodextrins in nasal delivery of low-molecular-weight heparins: in vivo and in vitro studies.

PURPOSE: To test the hypothesis that cyclodextrins reversibly enhance nasal absorption of low-molecular-weight heparins (LMWHs) and to investigate the mechanisms by which cyclodextrins enhance LMWH absorption via the nose. METHODS: Absorption of LMWHs was studied by measuring plasma anti-factor Xa activity after nasal administration of various LMWH formulations to anesthetized rats. In vivo reversibility studies were performed to investigate if the effects of cyclodextrins are reversible and diminish with time. The absorption-enhancing mechanisms of cyclodextrins were investigated in cell culture model. The transport of enoxaparin and mannitol, changes in transepithelial electrical resistance (TEER), and distribution of tight junction protein ZO-1 were investigated. RESULTS: Formulations containing 5% dimethyl-beta-cyclodextrin (DMbetaCD) produced the highest increase in the bioavailability of LMWH preparations tested. In vivo reversibility studies with 5% DMbetaCD showed that the effect of the absorption enhancer at the site of administration diminished with time. Transport studies using 16HBE14o(-) cells demonstrated that the increase in the permeability of enoxaparin and mannitol, reduction in TEER, and the changes in the tight junction protein ZO-1 distribution produced by 5% DMbetaCD were much greater than those produced by beta-cyclodextrin (betaCD) or hydroxyl-propyl-beta-cyclodextrin (HPbetaCD). CONCLUSIONS: Of the cyclodextrins tested, DMbetaCD was the most efficacious in enhancing absorption of LMWHs both in vivo and in vitro. The study also suggests that cyclodextrins enhance nasal drug absorption by opening of cell-cell tight junctions.

Administration, Intranasal↗
PubMed2002

Cyclodextrins in eye drop formulations: enhanced topical delivery of corticosteroids to the eye.

Cyclodextrins are cylindrical oligosaccharides with a lipophilic central cavity and hydrophilic outer surface. They can form water-soluble complexes with lipophilic drugs, which 'hide' in the cavity. Cyclodextrins can be used to form aqueous eye drop solutions with lipophilic drugs, such as steroids and some carbonic anhydrase inhibitors. The cyclodextrins increase the water solubility of the drug, enhance drug absorption into the eye, improve aqueous stability and reduce local irritation. Cyclodextrins are useful excipients in eye drop formulations of various drugs, including steroids of any kind, carbonic anhydrase inhibitors, pilocarpine, cyclosporins, etc. Their use in ophthalmology has already begun and is likely to expand the selection of drugs available as eye drops. In this paper we review the properties of cyclodextrins and their application in eye drop formulations, of which their use in the formulation of dexamethasone eye drops is an example. Cyclodextrins have been used to formulate eye drops containing corticosteroids, such as dexamethasone, with levels of concentration and ocular absorption which, according to human and animal studies, are many times those seen with presently available formulations. Cyclodextrin-based dexamethasone eye drops are well tolerated in the eye and seem to provide a higher degree of bioavailability and clinical efficiency than the steroid eye drop formulations presently available. Such formulations offer the possibility of once per day application of corticosteroid eye drops after eye surgery, and more intensive topical steroid treatment in severe inflammation. While cyclodextrins have been known for more than a century, their use in ophthalmology is just starting. Cyclodextrins are useful excipients in eye drop formulations for a variety of lipophilic drugs. They will facilitate eye drop formulations for drugs that otherwise might not be available for topical use, while improving absorption and stability and decreasing local irritation.

Administration, Topical↗
PubMed2001

Influence of cyclodextrin ring substituents on folding-related aggregation of bovine carbonic anhydrase.

A common obstacle to proper renaturation of an unfolded protein is aggregation, an intermolecular side reaction of immense importance in biotechnology and in the pathogenesis of several neurodegenerative diseases. Cyclic sugars known as cyclodextrins have been used as protein-folding aids. The effect of cyclodextrin chemistry on aggregation and refolding of carbonic anhydrase was evaluated in this study. Size-exclusion HPLC showed that cyclodextrins inhibit aggregate formation without interfering with the correct renaturation of carbonic anhydrase. PAGE of refolded enzyme provides further evidence of inhibition of folding-related aggregation by natural and chemically modified cyclodextrins. Although the amount of aggregate formed and recovery of active enzyme was dependent on cavity size, the nature of the chemical substituents found on the rims of the sugar molecule seems to play a more important role in cyclodextrin-assisted refolding of carbonic anhydrase. In general, neutral or cationic cyclodextrins with small cavities were found to be better folding aids than anionic cyclodextrins with larger holes. Although the exact prediction of the effect of a cyclodextrin substitution on protein refolding is not possible at present, these results clearly show that modified cyclodextrins can be designed that effectively inhibit protein aggregation.

Animals↗
PubMed2003

Structural background of cyclodextrin-protein interactions.

Cyclodextrins are cyclic oligosaccharides with the shape of a hollow truncated cone. Their exterior is hydrophilic and their cavity is hydrophobic, which gives cyclodextrins the ability to accommodate hydrophobic molecules/moieties in the cavity. This special molecular arrangement accounts for the variety of beneficial effects cyclodextrins have on proteins, which is widely used in pharmacological applications. We have studied the interaction between beta-cyclodextrin and four non-carbohydrate-binding model proteins: ubiquitin, chymotrypsin inhibitor 2 (CI2), S6 and insulin SerB9Asp by NMR spectroscopy at varying structural detail. We demonstrate that the interaction of beta-cyclodextrin and our model proteins takes place at specific sites on the protein surface, and that solvent accessibility of those sites is a necessary but not compelling condition for the occurrence of an interaction. If this behaviour can be generalized, it might explain the wide range of different effects of cyclodextrins on different proteins: aggregation suppression (if residues responsible for aggregation are highly solvent accessible), protection against degradation (if point of attack of a protease is sterically 'masked' by cyclodextrin), alteration of function (if residues involved in function are 'masked' by cyclodextrin). The exact effect of cyclodextrins on a given protein will always be related to the particular structure of this protein.

Cyclodextrins↗
PubMed2003

Antimicrobial activity of beta-lactam antibiotics against clinical pathogens after molecular inclusion in several cyclodextrins. A novel approach to bacterial resistance.

Recognition and uptake by specific cellular receptors and transport systems for cyclodextrins have been demonstrated. Based on this concept, natural and synthetically modified cyclodextrins were used as drug carriers. Several beta-lactam antibiotics were selected and their inclusion complexes with different cyclodextrins were prepared (molar ratio ranging from 1:1 to 1:3). The complex formation, in aqueous solution, was monitored and optimum complexation conditions were selected. The inclusion of the active molecules in the cyclodextrin cavity was confirmed by (1)H NMR spectroscopy. Specific HPLC methods for the quantitation of antibiotics in the presence of cyclodextrins were developed and their chemical stability under complexation conditions was confirmed. Antimicrobial activity of drug-cyclodextrin complexes, in terms of minimum inhibitory concentration (MIC), were compared with the corresponding values of uncomplexed free molecules. A wide range of clinical pathogens and known beta-lactamase-producing strains were tested. The activity of the cyclodextrin-included antibiotics was increased, particularly against Gram-negative clinical strains. The nature and degree of substitution on cyclodextrin macromolecules may be the predominant factor in the observed improvement in antimicrobial activity. We believe that the proposed methodology is a novel approach to the microbial resistance problem and will trigger research towards the development of new cyclodextrin derivatives bearing the ability to increase the uptake of included antimicrobial molecules through intensification of the corresponding molecular recognition phenomena.

Anti-Bacterial Agents↗
PubMed2005

[Solubilization and complexation of the antileukotrienic drug Quinlukast in aqueous solutions of cyclodextrins].

Solubility of the new antileukotrienic drug quinlukast (4-{[4-(2-quinolylmethoxy)phenyl]sulfanyl}benzoic acid) was determined in water and in aqueous solutions of alpha-cyclodextrin (alpha-CD), beta-cyclodextrin (beta-CD), hydroxypropyl-beta-cyclodextrin (HP-beta-CD, average degree of substitution 0.8), and methyl-beta-cyclodextrin (M-beta-CD, average degree of substitution 1.8). The determined solubility of quinlukast in water was 0.081 +/- 0.008 mmol/l (3.12 +/- 0.30 mg/100 ml) and only an insignificant increase in quinlukast solubility was observed in aqueous solutions of beta-CD. However, three well soluble cyclodextrins showed a marked solubilizing effect, in aqueous solutions with a moderate cyclodextrin concentration 5 g/100ml, a 12-fold increase in quinlukast solubility was observed in the case of M-beta-CD, and a 10-fold increase in the case of both HP-beta-CD and alpha-CD. Phase solubility diagrams of quinlukast in aqueous solutions of these cyclodextrins (up to 0.05 mol/l) were determined. In the cases of M-beta-CD and HP-beta-CD, the solubility diagrams were linear (AL) and they corresponded to the formation of a soluble inclusion complex quinlukast - cyclodextrin 1:1 with the evaluated stability constants K11 300 +/- 35 l/mol and 260 +/- 30 l/mol for M-beta-CD and HP-beta-CD, respectively. The phase solubility diagram of quinlukast in aqueous solutions of alpha-CD showed a marked positive deviation (AP) from linearity, the solubilization efficiency of dilute alpha-CD solutions was relatively low but it increased progressively with the increasing alpha-CD concentration. In the overall evaluation, the cyclodextrins alpha-CD, HP-beta-CD and M-beta-CD appeared to be suitable for the quinlukast solubilization into aqueous solutions.

Cyclodextrins↗
PubMed2005

Sulfoalkyl ether-alkyl ether cyclodextrin derivatives, their synthesis, NMR characterization, and binding of 6alpha-methylprednisolone.

The objective of this study is to see if random alkyl ethers of various sulfoalkyl ether cyclodextrins can be synthesized and characterized. The purpose of the alkylation was to test the hypothesis that an increase in the "height" of a cyclodextrins cavity would help in the binding/complexation of larger more structurally complex molecules. The synthesis of new cyclodextrin derivatives comprising a mixture of sulfoalkyl ether and alkyl ether substituents on the same cyclodextrin ring was performed in aqueous alkaline solutions using various sultones and alkylsulfates. The method presented provided an easy and efficient way to modify cyclodextrins avoiding the use of organic solvents and high quantities of alkylating agents and could be carried out in either a two step or "one pot" single step process. Purification was by neutralization followed by ultrafiltration. The derivatives were characterized by 1D, ((1)H and (13)C), and a 2D NMR technique (HMQC, Heteronuclear Multiple Quantum Coherence). The combination of these techniques allowed an analysis of the degree of substitution and the site of substitution on the cyclodextrin (CD) nucleus. For both beta- and gamma-CD, sulfoakylation was preferred on the 2 > 3 > 6 hydroxyls while alkylation was preferred 6 > 2 > 3. Due to the simultaneous presence of short alkyl ether chains and negatively charged sulfoalkyl ether chains, these mixed water-soluble cyclodextrin derivatives, especially those of gamma-cyclodextrin, should be able to bind more complex drugs. The improved binding capacity of these new modified CDs with the model drug 6alpha-methylprednisolone is reported.

Alkylation↗
PubMed1994

Effect of (hydroxypropyl)-beta-cyclodextrin on flux of morphine, fentanyl, sufentanil, and alfentanil through the spinal meninges of monkey.

Previous studies have demonstrated that (hydroxypropyl)-beta-cyclodextrin behaves as a slow-release reservoir when used as a vehicle for intrathecal administration of opioids. The goal of the current investigation was to determine if (hydroxypropyl)-beta-cyclodextrin might serve as a slow-release vehicle for epidural opioid administration as well. An in vitro diffusion cell model was used to determine the flux of morphine, fentanyl, alfentanil, and sufentanil through the spinal meninges of Macaque nemestrina monkeys in the absence or presence of varying concentrations of (hydroxypropyl)-beta-cyclodextrin. No concentration of cyclodextrin slowed the flux of any of the opioids through the meninges, indicating that (hydroxypropyl)-beta-cyclodextrin will not behave as a slow-release reservoir for these opioids in the epidural space. This finding suggests that the rate-limiting step in opioid transfer was diffusion through the meninges not dissociation of the opioid cyclodextrin complex. However, (hydroxypropyl)-beta-cyclodextrin significantly increased the flux of sufentanil through the meninges. Since sufentanil's hydrophobicity has previously been shown to impede its meningeal flux, this finding suggests that cyclodextrin effectively decreases sufentanil's hydrophobicity by formation of inclusion complexes in the aqueous environments of the spinal meninges.

2-Hydroxypropyl-beta-cyclodextrin↗