Usefulness Of Cyclodextrins Research Articles

Solid state characterization of the inclusion complex of valsartan with methyl β-cyclodextrin

In this work, we illustrate the usefulness of cyclodextrins, namely, methyl-β-cyclodextrin (MβCD), an amorphous, methylated derivative of the natural β-cyclodextrin, as a tool to form an inclusion complex with Valsartan (VAL), a poorly water soluble drug. The phase solubility study showed AL type of curve with slope less than one indicating the formation of complexes in 1:1 molar ratio of drug and CD. The stability constant was found to be 538.14 ± 5.4 Mole−1. Solid binary systems between VAL and MβCD were prepared experimentally in a stoichiometry 1:1 by different techniques (physical mixing, kneading, co-evaporation). Afterward these products were characterized by Fourier transform infrared spectroscopy (FTIR), Differential scanning calorimetry (DSC), Scanning electron microscopy (SEM) and 1H Nuclear magnetic resonance study (1H NMR). The results obtained suggested that co-evaporation methods yield a higher degree of amorphous entities suggesting the formation of inclusion complex between VAL and MβCD. The dissolution of VAL from the binary systems was studied to select the most appropriate system for the formulation development. It was concluded that the preparation technique played an important role in the dissolution behavior of the drug and the inclusion complex between VAL and MβCD obtained by co-evaporation method allowed better performance.

Preparation and physicochemical characterization of omeprazole:methyl-beta-cyclodextrin inclusion complex in solid state

In this work, we illustrate the usefulness of cyclodextrins, namely, methyl-β-cyclodextrin (MβCD), an amorphous, methylated derivative of the natural β-cyclodextrin (βCD), as a tool to form an inclusion complex with omeprazole (OME), a poorly water soluble drug. Solid binary systems between OME and MβCD were prepared experimentally in a stoichiometry 1:1 by different techniques (physical mixing, kneading, spray-drying and freeze-drying). Afterward these products were characterized by Fourier transformation-infrared spectroscopy (FTIR); X-ray diffractometry (XRD) and scanning electron microscopy (SEM). The results obtained suggest that spray-drying and freeze-drying methods yield a higher degree of amorphous entities suggesting the formation of inclusion complexes between OME and MβCD.

Sorption/Desorption of Polychlorinated Dibenzo-P-Dioxins and Polychlorinated Dibenzo Furans (PCDDs/PCDFs) in the Presence of Cyclodextrins

The goal of this study was to investigate the usefulness of cyclodextrins (CDs) for the removal of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzo furans (PCDDs/PCDFs) in soil and water. Five CDs having different molecular cavities and active functional groups were selected and evaluated for their ability to include (trap) PCDDs/PCDFs in soil and water. For the soil experiments, CDs were added to the soil on day one and the concentrations of unbound PCDDs/PCDFs were monitored over a 28-day period. Parallel control experiments were conducted to assist in the process performance evaluation. The ability of CDs to remove PCDDs/PCDFs from the contaminated soil was dependent upon the type of CD used and constituents of PCDDs/PCDFs. Among the five CDs investigated, hydroxypropyl-β -cyclodextrin (HPBCD) gave the highest removal efficiency for all components of PCDDs/PCDFs. The removal efficiency of total PCDDs/PCDFs was 81% one day after application of CDs and then increased to 96% after 28 days. The α -cyclodextrin (ACD) and β -cyclodextrin (BCD) removed only 45% and 50% of the total PCDDs/PCDFs after 28 days, respectively, whereas hydroxypropyl-γ -cyclodextrin (HPGCD) removed 80% of the total PCDDs/PCDFs.

Role of Cyclodextrins in Ophthalmics

Cyclodextrins are oligosaccharides having outer hydrophilic surface and central hydrophobic cavity. These agents form inclusion complexes with poorly water-soluble drugs; hence they show an important implication for use in ophthalmics because of their applications in solubilising and stabilising the ocular drugs. Most of the drugs being used in ophthalmics were not tailor-made for the eye and considering the poor bioavailability of <1% from the corneal surface, presentation of the drug in a soluble form and at high concentration is important. Provision of a high drug concentration at the corneal surface increases the percent drug permeation indicating the usefulness of cyclodextrins as penetration enhancers. A decrease in irritation potential of some drugs upon incorporation of cyclodextrins is also reported. Polymer-cyclodextrin multicomponent systems further extend the role of cyclodextrins in improving the solubility and bioavilability of ocular drugs. Large hydrophilic cyclodextrins like hydroxypropyl-beta-cyclodextrin and sulphobutylether-beta-cyclodextrin are safe for the use in aqueous eye drop solutions especially since they do not cross the lipophilic cornea. Various aspects about the applications of cyclodextrins in ophthalmics, the formulation considerations and expected toxicity of cyclodextrins (especially if high concentration is used) is discussed in this review. Strategies like use of polymers to reduce the effective concentration of cyclodextrin required without compromising solubility are also included. Further the concept of incorporating the drug-cyclodextrin complexes into liposomes or niosomes for a better targeting of the drug at appropriate tissue destination is discussed as a possible future option.

Characterization of inclusion complexes of betamethasone-related steroids with cyclodextrins using high-performance liquid chromatography

HPLC was used to study the inclusion complexes formed between various β- and γ-cyclodextrins and a series of corticosteroids related to betamethasone. Apparent association constants were measured in acetonitrile–water for a set of 13 steroids. An increase in the stability of the steroid–cyclodextrin complex is observed at lower concentrations of acetonitrile. The effects of the nature of the halide at the 9-position, the location of a double bond within the C-ring, substitution at the 9- and 11-positions, and modification of the D-ring of the steroid backbone were studied. The 11- and 17-positions were found to be critically involved in the inclusion process. Larger apparent association constants were obtained with γ-cyclodextrin (γ-CD) than with β-cyclodextrin (β-CD) due to the increased diameter of the γ-CD cavity. Van’t Hoff plots were constructed to examine the thermodynamic properties of the inclusion process. Plots constructed using retention factors were found to be nonlinear when γ-CD was present in the mobile phase. This is due to an increase in the strength of the inclusion complex as temperature decreases. Plots constructed using apparent association constants were linear, indicating that the mechanism of inclusion does not change over the range of temperatures studied (10 to 80°C). Enthalpy–entropy compensation was observed for 11 of the 13 steroids studied. The usefulness of cyclodextrins to achieve the separation of steroids in HPLC is discussed and a practical application for the analysis of a steroid and three potential impurities is described.

Usefulness of cyclodextrins for detection in molecular fluorescence. Application to xenobiotics and drugs

Cyclodextrins (CDs) present the unique ability to entrap molecules. In analytical chemistry, they have been mainly used for separation purpose. The present review deals with their potential interest towards the detection by molecular fluorescence of the included compounds mainly xenobiotics and drugs. As some of the included molecules exhibit native fluorescence due to their aromaticity, the addition to their aqueous solution of CDs entails, in some cases, a large enhancement of their emission of fluorescence. This feature appears of particular interest from an analytical point of view, either for direct detection of the guest molecule or as a detection mode after separations techniques (i.e.: chromatography or electrophoresis). Decrease in rotation motion of entrapped molecule and (or) decrease in solvent relaxation appear as the main causes of the enhancing emission effect. Some example picked up from pharmaceutical and bioanalytical literature are presented in order to demonstrate the interest of CDs in the field of the fluorescence techniques.

Alkalinizing Water-Soluble Local Anesthetic Solutions by Addition of Cyclodextrin

Background and objectivesThe use of sodium bicarbonate for alkalinization of local anesthetics to improve their efficacy has some disadvantages including decreased stability of the solutions. The present study was performed to evaluate usefulness of cyclodextrins (CDs) in improving the solubility and stability of local anesthetic solutions at near physiologic pH without precipitation.MethodsSolubility of local anesthetics with or without CDs in physiologic saline was investigated by monitoring cloudiness or precipitate formation visually and by recording absorbance at 620 nm. Interaction of anesthetic and CD was also studied spectrophotometrically using spectral change of the drugs associated with the inclusion complex formation.ResultsCyclodextrins improved the solubility and stability of the four local anesthetics studied (dibucaine, tetracaine, bupivacaine, and lidocaine). In the neutral pH region, the effects of the CDs were more significant with dibucaine and tetracaine, which are more hydrophobic than the other two. A type of effective CD was different for each anesthetic depending partly on the tendency to form inclusion complex with local anesthetic. The local anesthetic solutions solubilized by CDs were found to remain clear for more than 72 hours without any visible precipitation or turbidity at neutral pHs.ConclusionsThe improved solubility of local anesthetics by adding CD may be caused by inclusion complex formation of CD with local anesthetics. This new preparation for the alkalinized water-soluble anesthetic solutions may be useful for practical application in the clinical setting, although this awaits further study.

Alkalinizing water-soluble local anesthetic solutions by addition of cyclodextrin.

The use of sodium bicarbonate for alkalinization of local anesthetics to improve their efficacy has some disadvantages including decreased stability of the solutions. The present study was performed to evaluate usefulness of cyclodextrins (CDs) in improving the solubility and stability of local anesthetic solutions at near physiologic pH without precipitation. Solubility of local anesthetics with or without CDs in physiologic saline was investigated by monitoring cloudiness or precipitate formation visually and by recording absorbance at 620 nm. Interaction of anesthetic and CD was also studied spectrophotometrically using spectral change of the drugs associated with the inclusion complex formation. Cyclodextrins improved the solubility and stability of the four local anesthetics studied (dibucaine, tetracaine, bupivacaine, and lidocaine). In the neutral pH region, the effects of the CDs were more significant with dibucaine and tetracaine, which are more hydrophobic than the other two. A type of effective CD was different for each anesthetic depending partly on the tendency to form inclusion complex with local anesthetic. The local anesthetic solutions solubilized by CDs were found to remain clear for more than 72 hours without any visible precipitation or turbidity at neutral pHs. The improved solubility of local anesthetics by adding CD may be caused by inclusion complex formation of CD with local anesthetics. This new preparation for the alkalinized water-soluble anesthetic solutions may be useful for practical application in the clinical setting, although this awaits further study.

Co-administration of a water-soluble polymer increases the usefulness of cyclodextrins in solid oral dosage forms.

The aim of this study was to investigate the effect of cyclodextrins (beta-CD, HP-beta-CD and (SBE)7m-beta-CD), and co-administration of a water-soluble polymer (HPMC) and cyclodextrins, on the oral bioavailability of glibenclamide in dogs. Effects of cyclodextrins on the aqueous solubility of glibenclamide, with and without hydroxypropylmethylcellulose (HPMC), were determined by a phase-solubility method. Solid inclusion complexes were prepared by freeze-drying. Glibenclamide was administered orally and intravenously to beagle dogs. Aqueous solubility of glibenclamide increased as a function of cyclodextrin concentration, showing an AL-type diagram for beta-CD and an Ap-type diagrams for both of the beta-CD derivatives studied. HPMC enhanced the solubilising effect of cyclodextrins, but did not affect the type of phase-solubility diagram. Orally administered glibenclamide and its physical mixture with HP-beta-CD showed poor absolute bioavailability, while orally administered glibenclamide/cyclodextrin-complexes significantly enhanced the absolute bioavailability of glibenclamide. Orally administered glibenclamide/beta-CD/HPMC and glibenclamide/(SBE)7m-beta-CD/HPMC complexes showed similar absolute bioavailability compared to formulations not containing HPMC, even though 80% (in the case of (SBE)7m-beta-CD) or 40% (in the case of beta-CD) less cyclodextrin was used. The oral bioavailability of glibenclamide was significantly increased by cyclodextrin complexation. HPMC increased the solubilising effect of cyclodextrins and, therefore, the amount of cyclodextrin needed in the solid dosage form was significantly reduced by their co-administration. In conclusion, the pharmaceutical usefulness of cyclodextrins in oral administration may be substantially improved by co-administration of a water-soluble polymer.