IMPORTANCE OF CYCLODEXTRINS IN HUMAN

MEDICINE

A homologous group of cyclic glucans consisting of alpha-1,4 bound

glucoseunits obtained by the action of cyclodextrin glucanotransferase on starch or
similar substrates. The enzyme is produced by certain species of Bacillus.. Cyclodextrins
form inclusion complexes with a wide variety of substances.

• α -cyclodextrin: six membered sugar ring molecule

• β -cyclodextrin: seven sugar ring molecule
• γ -cyclodextrin: eight sugar ring molecule

History of cyclodextrins

Cyclodextrins, as they are known today, were called "cellulosine" when first described by
A. Villiers in 1891. Soon after, F. Schrödinger identified the three naturally occurring
cyclodextrins -α, -β, and -γ. These compounds were therefore referred to as "Schardinger
sugars". By the mid 1970's, each of the natural cyclodextrins had been structurally and
chemically characterized and many more complexes had been studied. Since the 1970s,
extensive work has been conducted by Szejtli and others exploring encapsulation by
cyclodextrins and their derivatives for industrial and pharmacologic applications.

Structure

γ-CD toroid structure showing spatial arrangement.

Cyclodextrins are constituted by 6-8 glucopyranoside units, can be topologically

represented as toroids with the larger and the smaller openings of the toroid exposing to
the solvent secondary and primary hydroxyl groups respectively. Because of this
arrangement, the interior of the toroids is not hydrophobic, but considerably less
hydrophilic than the aqueous environment and thus able to host other hydrophobic
molecules. In contrast, the exterior is sufficiently hydrophilic to impart cyclodextrins (or
their complexes) water solubility.
The formation of the inclusion compounds greatly modifies the physical and chemical
properties of the guest molecule, mostly in terms of water solubility. This is the reason
why cyclodextrins have attracted much interest in many fields, especially pharmaceutical
applications: because inclusion compounds of cyclodextrins with hydrophobic molecules
are able to penetrate body tissues, these can be used to release biologically active
compounds under specific conditions. In most cases the mechanism of controlled
degradation of such complexes is based on pH change of water solutions, leading to the
cleavage of hydrogen or ionic bonds between the host and the guest molecules.
Alternative means for the disruption of the complexes take advantage of heating or action
of enzymes able to cleave α-1,4 linkages between glucose monomers

Advantages

• Cyclodextrins are chemically and physically stable molecules formed by the

enzymatic modification of starch. They have the ability to form complexes with
a wide variety of organic compounds. As a result of Complexation of
compounds by cyclodextrins, the apparent solubility of the molecule can be
altered, the stability of the compound in the presence of light, heat and oxidizing
conditions is increased and volatility of compounds is decreased. Cyclodextrins
can also be used as processing aids to isolate compounds from natural sources
and to remove unwanted compounds .The major advantages of the application
of CD-Complexation in Pharmaceuticals, foods, cosmetics and toiletry are as
follows:

Protection of the active ingredient(s) against :

• Oxidation
• light induced reactions
• decomposition and thermal decomposition
• loss by evaporation and sublimation.

Elimination (or reduction) of :

• undesired tastes / odours

• microbiological contaminations
• fibres/other undesired components
• Hygroscopicity
Physical and Chemical Properties:

Cavity size
Table shows the dimensions of the alpha, beta and gamma Cyclodextrins. Dimensions, in
Angstroms, of the Cyclodextrins.

Inner Outer
CD Type Height
Diameter Diameter
Alpha CD 5.7 13.7 7.8
Beta CD 7.8 15.3 7.8
Gamma CD 9.5 16.9 7.8

The more interaction that occurs between the walls of the Cyclodextrin and the guest molecule, the
stronger is the binding.

Solubility of Cyclodextrins
This fundamental characteristic derives from the location of all free hydroxyl groups of each
successive glucose unit on rims of this donut shape molecules.

Thermal stability
Peaks of differential Scanning Calorimetry shows that Cyclodextrins are heat stable.

Hygroscopicity
Cyclodextrins are not hygroscopic and remain a dry pourable powder at the equilibrium
moisture (10 – 14 % water ) .

Chemical stability
Cyclodextrins undergo acid hydrolysis with strong acids such as hydrochloric or sulfuric acid.
Weak acids, such as organic acids, do not hydrolyze cyclodextrins. However, hydrolysis with citric
acid has been observed in case of beta Cyclodextrin. Bases do not hydrolyze Cyclodextrins.

Enzymatic stability
Cyclodextrins are hydrolyzed by Cyclodextrin glucosyltransferase. Glucoamylases and beta
amylases do not hydrolyze cyclodextrins. Many alpha amylases will hydrolyze Cyclodextrins

Toxicology and metabolism

Alpha and beta Cyclodextrin are resistant to salivary and pancreatic amylases. As a result, they
pass through the digestive system to the colon intact. Various other toxicological tests including
dermal irritation, ocular irritation, inhalation, mutagenicity, Ames test, chromosomal aberration,
and teratology have shown no adverse effects of b-Cyclodextrin. While GRAS petitions for use of
b-Cyclodextrin are still pending at the Food and Drug Administration in the United States, it is
already approved as an food additive in countries including West Germany, France, Japan, China,
Hungary, Netherlands, Luxembourg, Belgium and Spain. Cyclodextrins are non-reducing.

Cyclodextrins are stable toward alkalis, even at elevated temperatures

 IMPORTANCE:

Cyclodextrins are able to form host-guest complexes with hydrophobic

molecules given the unique nature imparted by their structure. As a result, these molecules have
found a number of applications in a wide range of fields. Other than the above mentioned
pharmaceutical applications for drug release, cyclodextrins can be employed in environmental
protection: these molecules can effectively immobilise inside their rings toxic compounds, like
trichloroethane or heavy metals, or can form complexes with stable substances, like trichlorfon (an
organophosphorus insecticide) or sewage sludge, enhancing their decomposition.

In the food industry cyclodextrins are employed for the preparation of

cholesterol free products: the bulky and hydrophobic cholesterol molecule is easily lodged inside
cyclodextrin rings that are then removed.Weight loss supplements are marketed from alpha-
cyclodextrin which claim to bind to fat and be an alternative to other anti-obesity medications

Other food applications further include the ability to stabilize volatile or

unstable compounds and the reduction of unwanted tastes and odour. Reportedly cyclodextrins are
used in alcohol powder, a powder for mixing alcoholic drinks.

The strong ability of complexing fragrances can also be used for another
purpose: first dry, solid cyclodextrin microparticles are exposed to a controlled contact with fumes
of active compounds, then they are added to fabric or paper products. Such devices are capable of
releasing fragrances during ironing or when heated by human body. Such a device commonly used
is a typical 'dryer sheet'. The heat from a clothes dryer releases the fragrance into the clothing.

The ability of cyclodextrins to form complexes with hydrophobic molecules

has led to their usage in supramolecular chemistry. In particular they have been used to synthesize
certain mechanically-interlocked molecular architectures, such as rotaxanes and catenanes, by
reacting the ends of the threaded guest.

CONCLUSION:

As the Cyclodextrins has wider applications and advantages in present scenario,the

usage of Cyclodextrin inclusion complexes has been increasing day by day ,hence it can be
conclude that cyclodextrins had major importance in preparation of human medicine.
 Document By
SANTOSH BHARADWAJ REDDY
Email: help@matlabcodes.com
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