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Frequently Asked Questions
What are cyclodextrins (CDs)?
Cyclodextrins are cyclic oligosaccharides consisting of α-1,4-glucopyranose units. The main representatives are alpha-, beta- and gamma-CDs with 6-8 glucose units, respectively. Due to their relatively lipophilic central cavity, they can physically include other molecules. Typical guest molecules are apolar and fit the cavity, like key and hole.
Are cyclodextrins synthetic or natural products?
Cyclodextrins can be found in nature. Some bacteria (e.g.
) produce CDs from starch by enzymatic process for their energy storage. This process is mimicked by the industry using
enzyme and starch (corn, potato, manioc, etc) as raw material. The so-called native CDs (alpha-, beta-, gamma-CDs) are considered natural. To change the properties of native CDs, synthetic CD derivatives are also produced from them via chemical modification.
Are cyclodextrins toxic?
In general native CDs have favorable toxicological profiles. There are numerous food products on the market containing native CDs, beta-cyclodextrin is even listed as E459 as a common food additive. However, depending on the region and the intended use some restrictions apply. Five CD derivatives (the native alpha-, beta-, gamma-CDs as well as hydroxypropylated-beta-CD and sulfobutylated-beta-CD) are listed in the US, EP and JP Pharmacopoeias and are widely used in pharmaceutical formulations (in over 40 approved drug formulations so far).
What is the inclusion complex and what is the driving force of complex formation?
All CDs have a relatively lipophilic cavity. Within the cavity they can entrap other molecules by physical, non-covalent and reversible forces (e.g. van der Waals forces, hydrogen bonds). Typical guest molecules are apolar and fit the cavity, like key and hole. The main driving force of the complex formation in aqueous medium is that the high-enthalpy water molecules in the CD-cavity are replaced with the guest molecule. No covalent bonds are formed between the host and the guest. The complex formation and dissociation are dynamic equilibrium processes. The formed complex dissociates to its original constituents unchanged.
What are the advantages of CD complexation?
Improvement of physical and chemical stability (volatile, oxygen-, light- and heat sensitive compounds)
Reduction of undesirable tastes and odors
Increased solubility in water
Stable aqueous solutions of insoluble compounds can be prepared without the use of organic co-solvents or surfactants
Enhanced rate of dissolution
Liquids can be transformed into solid form
Extended release of compounds
Alleviation of local irritaions (reduced side effects)
Incompatible compounds can be mixed and used together in complexed form
Stabilization of emulsions and suspensions
How can the CD complexes be prepared?
There are various ways to prepare the complexes in solid form. Just to name a few: by mechanical activation, kneading, co-crystallization, as well as by making aqueous common solution, or suspension. Usually the final step of the process is the removal of water. Considerable experience and some developmental work is required to find the ideal method for the complexation: the properties of the host and the guest molecule need to be taken into consideration.
What are the typical guest compounds?
Numerous organic or inorganic compounds form inclusion complexes with CDs. Guest compounds can be gases, liquids and solids as well. Concerning their application, these can be pharmaceuticals, vitamins, food additives, pesticides, aroma compounds, fragrances, etc. Due to the wide variety of cyclodextrin derivatives (in cavity size, charge and substituents - hundreds of derivatives) the number of guest compounds suitable for complexation is immerse.
Why use synthetic CD derivatives instead of native CDs?
Beta-CD has a limited water solubility (1.8% at room temperature). Using proper derivatization, products of highly enhanced solubility can be manufactured. Industrially produced modified CDs are hydroxypropyl-, sulfobutyl- and methyl-beta-CDs (HPBCD, SBECD, RAMEB), which are randomly substituted derivatives. They are mixtures of millions of compounds having similar structure.
Some CD-derivatives are single isomers (may be characterized by an exact formula): per- and monosubstituted CDs.
Regarding the type of substituents, there are ionic (such as SBECD, Quaternary amino CDs, etc.) and non-ionic (TRIMEB, HPBCD, etc) derivatives. Some special derivatives have been developed for biological applications (e.g. fluorescent derivatives). For further examples see
What are CD polymers?
CDs can be coupled to each other or to a macromolecular scaffold by chemical crosslinking. Different CD polymers (water soluble or swelling) can be produced depending on the manufacturing conditions. The cavity size of CDs are not influenced by the crosslinking process, therefore these remain open for inclusion complex formation. The application of these nanostructures is based on the cooperativity of the adjacent rings. These polymers can be widely used (pharmaceutical industry, environmental biotechnology, etc).