1
Thomas Mavromoustakos et al. (eds.), Supramolecules in Drug Discovery and Drug Delivery: Methods and Protocols,
Methods in Molecular Biology, vol. 2207, https://doi.org/10.1007/978-1-0716-0920-0_1,
© Springer Science+Business Media, LLC, part of Springer Nature 2021
Chapter 1
Application of Neutralization and Freeze-Drying Technique
for the Preparation of the Beneficial in Drug Delivery
2-Hydroxypropyl-β-Cyclodextrin Complexes with Bioactive
Molecules
Eirini Christodoulou, Dimitrios Ntountaniotis, Georgios Leonis,
Thomas Mavromoustakos, and Georgia Valsami
Abstract
Bioavailability of active substances is of great importance for the formulation of a drug product, as it actually reflects drug absorption and achievement of the optimum pharmacological effect. A great number of
chemical compounds with excellent pharmacological properties possess low solubility and permeability
values, ending in low bioavailability in the human body after administration (especially after per os administration). CDs are oligosaccharides that possess biological properties similar to their linear counterparts,
but some of their physicochemical properties differ. They are enhancing bioavailability and solving problems of absorption for poorly soluble lipophilic drugs by forming water-soluble inclusion complexes. For
this reason, they are widely used in drug delivery systems (Carrier et al. J Control Release 123:78–99,
2007; Kurkov and Loftsson, Int J Pharm 453:167–80, 2013). The main purpose of this chapter is to show
a protocol for the preparation of drug:CD complex delivery systems.
Key words Cyclodextrins, 2-Hydroxypropyl-β-CD, Methyl-β-CD, Bioavailability, Lyophilization,
Inclusion complex
1 Introduction
Cyclodextrins (CDs) are a-(1,4)-linked cyclic oligosaccharides
containing glucopyranose units. The glucopyranose units possess
chair conformation, due to which CDs are not cylindrical, and
exhibit torus-like shape (truncated cone), in which the primary
hydroxyl groups are present on narrow edge and secondary
hydroxyl groups are on the wider edge of the cone in the outer
surface. In the interior of the CD molecule, skeletal carbons with
hydrogen atoms and oxygen bridges are present leading to hydrophilic outer surface and lipophilic central cavity of CD [1–3].
Thomas Mavromoustakos et al. (eds.), Supramolecules in Drug Discovery and Drug Delivery: Methods and Protocols,
Methods in Molecular Biology, vol. 2207, https://doi.org/10.1007/978-1-0716-0920-0_1,
© Springer Science+Business Media, LLC, part of Springer Nature 2021
Chapter 1
Application of Neutralization and Freeze-Drying Technique
for the Preparation of the Beneficial in Drug Delivery
2-Hydroxypropyl-β-Cyclodextrin Complexes with Bioactive
Molecules
Eirini Christodoulou, Dimitrios Ntountaniotis, Georgios Leonis,
Thomas Mavromoustakos, and Georgia Valsami
Abstract
Bioavailability of active substances is of great importance for the formulation of a drug product, as it actually reflects drug absorption and achievement of the optimum pharmacological effect. A great number of
chemical compounds with excellent pharmacological properties possess low solubility and permeability
values, ending in low bioavailability in the human body after administration (especially after per os administration). CDs are oligosaccharides that possess biological properties similar to their linear counterparts,
but some of their physicochemical properties differ. They are enhancing bioavailability and solving problems of absorption for poorly soluble lipophilic drugs by forming water-soluble inclusion complexes. For
this reason, they are widely used in drug delivery systems (Carrier et al. J Control Release 123:78–99,
2007; Kurkov and Loftsson, Int J Pharm 453:167–80, 2013). The main purpose of this chapter is to show
a protocol for the preparation of drug:CD complex delivery systems.
Key words Cyclodextrins, 2-Hydroxypropyl-β-CD, Methyl-β-CD, Bioavailability, Lyophilization,
Inclusion complex
1 Introduction
Cyclodextrins (CDs) are a-(1,4)-linked cyclic oligosaccharides
containing glucopyranose units. The glucopyranose units possess
chair conformation, due to which CDs are not cylindrical, and
exhibit torus-like shape (truncated cone), in which the primary
hydroxyl groups are present on narrow edge and secondary
hydroxyl groups are on the wider edge of the cone in the outer
surface. In the interior of the CD molecule, skeletal carbons with
hydrogen atoms and oxygen bridges are present leading to hydrophilic outer surface and lipophilic central cavity of CD [1–3].