Cyclodextrins (CyDs) are cyclic carbohydrates derived from starch. The parent CyDs contain six, seven and eight glucopyranose units and are referred as α-, β- and γ-CyD, respectively. The most important property of the CyDs is the ability to establish specific interactions - molecular encapsulation - with various types of molecules through the formation of non-covalently bonded entities, either in the solid phase or in aqueous solution. These nano-encapsulating agents may form inclusion complexes with essential oils and volatiles, or their components, in order to improve their characteristics, such as transformation of liquid compounds into crystalline form; masking unpleasant smells and tastes of some compounds; improving the physical and/or chemical stability; and stabilizing volatile compounds by reducing or eliminating any losses through evaporation. Complexation has been used to avoid the destruction of certain flavours by processing or, on storage, allowing the use of minor amounts of flavours. The guest molecule is released in the warm moisture of the mouth. Examples are spices, essential oils of vegetable origin and plant flavours, chamomile oil and extract, eucalyptus oil, fennel oil, lemon oil, onion and garlic oil, camphor, menthol, thymol, etc. There are several methods for the preparation of inclusion complexes; kneading, co-precipitation, freeze-drying and spray-drying the most commonly used. Evidence for a guest inclusion into the apolar CyD cavity may be proved by various analytical techniques, including NMR spectroscopy, UV-visible absorption spectroscopy, optical rotatory dispersion and circular dichroism, fluorescence, infrared/FT-IR spectroscopy, thermo-analysis, TLC, mass spectromety, and powder X-ray diffractometry. Copyright © 2010 John Wiley & Sons, Ltd.

A review on cyclodextrin encapsulation of essential oils and volatiles

Since the discovery of the crown ethers by Pedersen twenty years ago, the chemistry of synthetic hosts for the selective complexation of organic and inorganic guests has seen an extraordinarily rapid development. This article discusses in particular the contributions provided by synthetic cyclophanes as hosts to the understanding of molecular complexation of neutral organic guest molecules in aqueous and organic solvents. In aqueous solution, cyclophanes form stoichiometric complexes with neutral aromatic guests which can approach enzyme-substrate complexes in their stability. Efficient molecular complexation is also observed in organic environments. Here, as a result of large solvation effects, the strength of complexation is strongly dependent on the nature of the organic solvent. Electron donor-acceptor interactions can contribute significantly to the stability of complexes formed between cyclophane hosts and aromatic guests. Force-field calculations together with computer graphics are powerful tools in the design of water-soluble, optically active hosts for chiral recognition of complexed racemic guests. Simple and selective functionalization of the cyclophane framework leads to stable, bioorganic catalysts. Like enzymes, these catalysts bind their substrates in a rapid equilibrium prior to the reaction steps. As a perspective, some fascinating research objectives in the field of molecular recognition and catalysis which can be targeted with designed cyclophane hosts are shown.

Complexation of Neutral Molecules by Cyclophane Hosts

The ice nucleation temperature determines the primary drying rate of lyophilization for samples frozen on a temperature-controlled shelf.

Nanostructured lipid carrier (NLC) is second generation smarter drug carrier system having solid matrix at room temperature. This carrier system is made up of physiological, biodegradable and biocompatible lipid materials and surfactants and is accepted by regulatory authorities for application in different drug delivery systems. The availability of many products in the market in short span of time reveals the success story of this delivery system. Since the introduction of the first product, around 30 NLC preparations are commercially available. NLC exhibit superior advantages over other colloidal carriers viz., nanoemulsions, polymeric nanoparticles, liposomes, SLN etc. and thus, have been explored to more extent in pharmaceutical technology. The whole set of unique advantages such as enhanced drug loading capacity, prevention of drug expulsion, leads to more flexibility for modulation of drug release and makes NLC versatile delivery system for various routes of administration. The present review gives insights on the definitions and characterization of NLC as colloidal carriers including the production techniques and suitable formulations. This review paper also highlights the importance of NLC in pharmaceutical applications for the various routes of drug delivery viz., topical, oral, pulmonary, ocular and parenteral administration and its future perspective as a pharmaceutical carrier.

Nanostructured lipid carriers system: Recent advances in drug delivery

Hydroxypropyl-β-cyclodextrin: preparation and characterization; effects on solubility of drugs

The water vapor sorption isotherms have been established for α-, β-, and γ-cyclodextrin at 40°C. The powder X-ray diffraction patterns of crystal forms of cyclodextrins stored at various levels of relative humidity (RH) were examined and the results are discussed in terms of the hydration numbers. α-Cyclodextrin hydrate was stable at RH as low as 11%. The water vapor desorption isotherm of β-cyclodextrin showed pronounced hysteresis, which extended to lower RH.The hydrate form of β-cyclodextrin was stable over a wide range of RH in the desorption process, like that of α-cyclodextrin. The crystal form of γ-cyclodextrin 7H2O was obtaiend in addition to the dehydrate form and the 17H2O hydrate form.

Properties of Crystal Water of α-, β-, and γ-Cyclodextrin

A new method for preparing a solid inclusion compound was developed. A physical mixture of benzoic acid and α-or β-cyclodextrin (CD) or the ground mixture was sealed in a container after adsorbing a definite amount of water vapor, then heated to a temperature ranging from 43 to 142 °C. The results of powder X-ray diffraction and infrared spectroscopy showed that the crystalline inclusion compound was produced when the container was heated at over 70°C. The combining molar ratio of benzoic acid to α-CD in the inclusion compound prepared by this method was higher than that obtained by the coprecipitation method. Physical mixtures of benzoic acid and α-or β-CD were also sealed in a stainless steel vessel under nitrogen gas pressure, then heated to 127 °C. The pressurized samples had a higher combination ratio than the non-pressurized samples.

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New Methods for Preparing Cyclodextrin Inclusion Compounds. I. Heating in a Sealed Container

The extensively used antibacterial agent acrinol is known to form a monohydrate phase (H) on crystallization from water. We demonstrate here that acrinol also forms two anhydrous polymorphs, denoted form I (AI) and form II (AII). Polymorph AI is obtained directly on heating H, by a solid-state dehydration process, and polymorph AII is obtained subsequently from AI, by a polymorphic transformation. The crystal structures of AI and AII have been determined directly from powder X-ray diffraction data, employing the direct-space genetic algorithm technique for structure solution, followed by Rietveld refinement. From the structural properties of AI and AII, mechanistic aspects of the dehydration process and the polymorphic transformation have been established. From measurements of initial dissolution rates and enthalpies of dissolution, AII is assigned as the thermodynamically stable polymorph, with a monotropic relationship between AI and AII. The hydration properties of AI and AII differ significantly, with...

Physicochemical Understanding of Polymorphism and Solid-State Dehydration/Rehydration Processes for the Pharmaceutical Material Acrinol, by Ab Initio Powder X-ray Diffraction Analysis and Other Techniques

Aspirin, benzoic acid and p-hydroxybenzoic acid, all of which form intermolecularly hydrogen-bonded dimer structures in the crystalline form, were ground with α- or β-cyclodextrin. Inclusion compounds were also prepared by the coprecipitation method, except in the case of the aspirin-α-cyclodextrin system. The dispersed state of the medicinal molecules were investigated by analysis of the infrared spectra in the carbonyl stretching regions. It was suggested that the dispersed state of medicinals in the α-cyclodextrin system was different from that in the β-cyclodextrin system. It was assumed that, by grinding, aspirin molecules were included in the cyclodextrin cavity in the β-cyclodextrin system, but were dispersed monomolecularly in the hydrogen-bonded network structure of cyclodextrin in the α-cyclodextrin system. Interaction between medicinals and α- or β-cyclodextrin in aqueous solution was investigated by means of nuclear magnetic resonance studies. The sublimation of p-hydroxybenzoic acid from the ground mixtures or inclusion compounds with α- or β-cyclodextrin systems was determined by thermogravimetry. The effects of cyclodextrin on the hydrolysis of aspirin under acidic conditions were investigated as well.

Katsuhide Terada

Papers

Properties of Crystal Water of α-, β-, and γ-Cyclodextrin

New Methods for Preparing Cyclodextrin Inclusion Compounds. I. Heating in a Sealed Container

Physicochemical Understanding of Polymorphism and Solid-State Dehydration/Rehydration Processes for the Pharmaceutical Material Acrinol, by Ab Initio Powder X-ray Diffraction Analysis and Other Techniques

The Dispersed States of Medicinal Molecules in Ground Mixtures with α- or β-Cyclodextrin

Interaction of Medicinals and Porous Powder. I. Anomalous Thermal Behavior of Porous Glass Mixtures