3
amount of cyclodextrin is dissolved in water and the guest
active ingredient, dissolved in an organic solvent, is gradually
added in the solution under continuous stirring. The solution
is cooled and complex precipitate as a final product is formed,
collected washed with another solvent or water and dried.
(b) Slurry complexation
In order to prepare the complex, it is not necessary for the
cyclodextrin to be completely dissolved. Cyclodextrin can be
added to water at a concentration of 50–60% w/v in solid
form and then stirred. The aqueous phase will be saturated
with cyclodextrin in solution. Guest molecules will complex
with the cyclodextrin in solution and, as the cyclodextrin complex saturates the water phase, the complex will be crystallized
or precipitate out of the aqueous phase. The cyclodextrin crystals will be dissolved and continue to saturate the aqueous
phase to form the complex and precipitate or crystallize out of
the aqueous phase. The complex can be collected in the same
manner as with the coprecipitation method.
(c) Kneading method: paste complexation
A small amount of water is added to the cyclodextrin along
with the active ingredient in order to form a paste, using a
mortar and pestle or (on a large scale) using a kneader. The
time required is dependent on the guest molecule. The resulting complex can be dried directly or washed with a small
amount of water to remove the non-complexed particles that
are adsorbed on the cyclodextrin surface and collected by filtration or centrifugation to be dried under vacuum. Pastes will
sometimes get dry forming a hard mass instead of a fine powder. This is dependent on the guest molecule and the amount
of water used in the paste.
(d) Damp mixing and heating in a sealed container
The guest and cyclodextrin molecules are thoroughly mixed
and after adsorbing a definite amount of water vapor are placed
in a sealed container. The amount of water used in the method
can range between the amount of water of hydration in the
cyclodextrin and added guest to up to 20–25% water on a dry
basis. The sealed container and its contents are heated to about
100 °C and then the contents are removed and dried. The
amount of water added, the degree of mixing and the heating
time have to be optimized for each guest.
(e) Extrusion
Extrusion is a variation of the heating and mixing method
and is a continuous system. Cyclodextrin, guest molecule and
water can be premixed or mixed as added to the extruder.
Degree of mixing and amount of heating and time can be controlled in the barrel of the extruder. Depending upon the
Neutralization and Freeze-Drying Technique to Prepare Drug: CD Complexes
amount of cyclodextrin is dissolved in water and the guest
active ingredient, dissolved in an organic solvent, is gradually
added in the solution under continuous stirring. The solution
is cooled and complex precipitate as a final product is formed,
collected washed with another solvent or water and dried.
(b) Slurry complexation
In order to prepare the complex, it is not necessary for the
cyclodextrin to be completely dissolved. Cyclodextrin can be
added to water at a concentration of 50–60% w/v in solid
form and then stirred. The aqueous phase will be saturated
with cyclodextrin in solution. Guest molecules will complex
with the cyclodextrin in solution and, as the cyclodextrin complex saturates the water phase, the complex will be crystallized
or precipitate out of the aqueous phase. The cyclodextrin crystals will be dissolved and continue to saturate the aqueous
phase to form the complex and precipitate or crystallize out of
the aqueous phase. The complex can be collected in the same
manner as with the coprecipitation method.
(c) Kneading method: paste complexation
A small amount of water is added to the cyclodextrin along
with the active ingredient in order to form a paste, using a
mortar and pestle or (on a large scale) using a kneader. The
time required is dependent on the guest molecule. The resulting complex can be dried directly or washed with a small
amount of water to remove the non-complexed particles that
are adsorbed on the cyclodextrin surface and collected by filtration or centrifugation to be dried under vacuum. Pastes will
sometimes get dry forming a hard mass instead of a fine powder. This is dependent on the guest molecule and the amount
of water used in the paste.
(d) Damp mixing and heating in a sealed container
The guest and cyclodextrin molecules are thoroughly mixed
and after adsorbing a definite amount of water vapor are placed
in a sealed container. The amount of water used in the method
can range between the amount of water of hydration in the
cyclodextrin and added guest to up to 20–25% water on a dry
basis. The sealed container and its contents are heated to about
100 °C and then the contents are removed and dried. The
amount of water added, the degree of mixing and the heating
time have to be optimized for each guest.
(e) Extrusion
Extrusion is a variation of the heating and mixing method
and is a continuous system. Cyclodextrin, guest molecule and
water can be premixed or mixed as added to the extruder.
Degree of mixing and amount of heating and time can be controlled in the barrel of the extruder. Depending upon the
Neutralization and Freeze-Drying Technique to Prepare Drug: CD Complexes