49
1.4.3 Inclusion Phenomena and Its Effects
Since Cramer’s discovery of inclusion phenomena, effort was devoted to physical
and chemical properties of inclusion complexes and their consequences. Indeed, his
results were not only of fundamental interest but also of industrial interest, and in
the 1970s, this interest has grown considerably. Numerous works showed that inclusion of a guest active ingredient molecule in a host cyclodextrin molecule was a real
molecular encapsulation, and the resulting inclusion complex superstructure had
new physicochemical properties, stability, solubility, and also better therapeutic
efficacy. So, several technological characteristics used in pharmacy could also be
advantageously modified.
Rapidly, the pharmaceutical industry understood the advantages of using cyclodextrins. Szejtli (1982a, 1988) summarized them in six points:
1. The modification of the physicochemical properties of the guest molecule: e.g.,
liquid compounds can be transformed into crystalline, compressible forms; substances with low solubility in water become more soluble after complexation;
the rate of dissolution of poorly soluble substances can also be increased; certain
unpleasant tastes can be eliminated; smell can also be covered by complex forming; the color of certain substances can be altered since inclusion can change the
spectral properties of the guest; etc.
2. The modification of the chemical activity of the guest: e.g., reactive substances
can be protected by inclusion reducing the risks when they are mixed with other
substances; chemical reactions can be carried out selectively, the cyclodextrins
playing the role of catalysts; etc.
3. The stabilization of substances sensitive to light or to oxygen, etc., e.g., protection of active ingredients against oxidation, heat-promoted decomposition, or
light-induced reactions.
4. The uptake of volatile substances: e.g., volatile drug can be stabilized without
losses through evaporation; storage and handling of certain toxic substances
such as pesticides can be improved; savings can be made on the quantity of substance required owing to reduced evaporation; etc.
5. The complexation, extraction, and transport of pollutants.
6. Several technological advantages, e.g., stable, standardized compositions, simple dosage and handling of dry powders, reduced packing and storage costs, and
also saving of energy and manpower.
1.4.4 Large Cyclodextrins
Although the existence of cyclodextrins with over 8 glucose units is described and
studied for the first time in the 1950s by Freudenberg, French, and Cramer, it was
only in the middle of the 1990s that the cyclodextrins containing 9, 10, 11, and
12 units of glucose, called large-ring cyclodextrins, were studied in any depth
1 History of Cyclodextrins
1.4.3 Inclusion Phenomena and Its Effects
Since Cramer’s discovery of inclusion phenomena, effort was devoted to physical
and chemical properties of inclusion complexes and their consequences. Indeed, his
results were not only of fundamental interest but also of industrial interest, and in
the 1970s, this interest has grown considerably. Numerous works showed that inclusion of a guest active ingredient molecule in a host cyclodextrin molecule was a real
molecular encapsulation, and the resulting inclusion complex superstructure had
new physicochemical properties, stability, solubility, and also better therapeutic
efficacy. So, several technological characteristics used in pharmacy could also be
advantageously modified.
Rapidly, the pharmaceutical industry understood the advantages of using cyclodextrins. Szejtli (1982a, 1988) summarized them in six points:
1. The modification of the physicochemical properties of the guest molecule: e.g.,
liquid compounds can be transformed into crystalline, compressible forms; substances with low solubility in water become more soluble after complexation;
the rate of dissolution of poorly soluble substances can also be increased; certain
unpleasant tastes can be eliminated; smell can also be covered by complex forming; the color of certain substances can be altered since inclusion can change the
spectral properties of the guest; etc.
2. The modification of the chemical activity of the guest: e.g., reactive substances
can be protected by inclusion reducing the risks when they are mixed with other
substances; chemical reactions can be carried out selectively, the cyclodextrins
playing the role of catalysts; etc.
3. The stabilization of substances sensitive to light or to oxygen, etc., e.g., protection of active ingredients against oxidation, heat-promoted decomposition, or
light-induced reactions.
4. The uptake of volatile substances: e.g., volatile drug can be stabilized without
losses through evaporation; storage and handling of certain toxic substances
such as pesticides can be improved; savings can be made on the quantity of substance required owing to reduced evaporation; etc.
5. The complexation, extraction, and transport of pollutants.
6. Several technological advantages, e.g., stable, standardized compositions, simple dosage and handling of dry powders, reduced packing and storage costs, and
also saving of energy and manpower.
1.4.4 Large Cyclodextrins
Although the existence of cyclodextrins with over 8 glucose units is described and
studied for the first time in the 1950s by Freudenberg, French, and Cramer, it was
only in the middle of the 1990s that the cyclodextrins containing 9, 10, 11, and
12 units of glucose, called large-ring cyclodextrins, were studied in any depth
1 History of Cyclodextrins