Effect of Cyclodextrin Derivatization on Solubility and Efficacy of Drugs

Abstract

Cyclodextrins (CDs) possess cyclic structure having (α-1,4)-linked glucopyranose units making them less vulnerable to enzymatic degradation as than the linear dextrins. Commonly used natural CDs are α-CD, β-CD, and ɣ-CD with truncated cone-like appearance having lipophilic central cavity and hydrophilic exterior surface. The problem of low aqueous solubility of natural CDs can be addressed by reacting them with various reagents to produce water-soluble derivatives. CD derivatives can be categorized in many ways depending upon their substituents, biological activity, polarity, and size. The derivatization of natural CDs produces noncrystalline and amorphous forms with higher water solubility that are physically and microbiologically stable for prolonged time period. Variety of methods can be used to determine average degree of substitution for a modified CD. Dissociation by dilution is considered as major release mechanism of drugs from complex. It is essential to optimize the amount of CDs for a given preparation because they can either retard or promote drug delivery through biological membrane.

Incorporation of Inclusion Complexes in the Dissolvable Microneedle Ocular Patch System for the Efficiency of Fluconazole in the Therapy of Fungal Keratitis

“…This point is caused by the crystal natural CD (α-CD, β-CD, and γ-CD) having strong molecular bounding such as high crystal lattice energy which leads to low solubility. 51 Furthermore, derivative CD for instance SB-β-CD and HP-γ-CD are more soluble than natural CD due to the attachment of substituent from derivatives CD will disrupt the regular hydrogen bonding network within natural CD molecules that can enhance the water solubility by increasing their ability to interact with the surrounding water molecules. Particularly, SB-β-CD anionic alkyl chains form an extremely hydrophilic exterior surface which anionic chains provide for electrostatic repulsion that leads to the extension of the hydrophobic central cavity and amplifies the solubility in water.…”

“…In addition, SB-β-CD is a β-CD derivative compound that is polyanionic and highly hydrophilic, which is even more hydrophilic than β-CD and other derivatives. This point is caused by the crystal natural CD (α-CD, β-CD, and γ-CD) having strong molecular bounding such as high crystal lattice energy which leads to low solubility . Furthermore, derivative CD for instance SB-β-CD and HP-γ-CD are more soluble than natural CD due to the attachment of substituent from derivatives CD will disrupt the regular hydrogen bonding network within natural CD molecules that can enhance the water solubility by increasing their ability to interact with the surrounding water molecules.…”

Controlling the Solubility, Release Rate and Permeation of Riluzole with Cyclodextrins

“…Since the complexation constant for β-CD is essentially greater than that of α-CD, the size of the hydrophobic cavity of the first is more suitable to include the RLZ molecule. The greater value of the association constant with SBE-β-CD (and also HP-β-CD and DM-β-CD) as compared to β-CD makes evident that derivatization of natural CD produces more stable complexes [ 54 ]. Concerning SBE-β-CD, it has been recently reported [ 55 ] that the charged sulfonate groups of SBE-β-CD molecules are likely to repel one another by extending out and away from each other, providing an additional hydrophobic region near the cavity composed of only the alkyl ether moieties of the sulfobutyl groups.…”

Design of a Cyclodextrin Bioproduction Process Using Bacillus pseudofirmus and Paenibacillus macerans

“…These complexes offer protection to the guest Future Pharmacol. 2023, 3 569 molecules from various chemical and reactive species that could otherwise cause their degradation [7][8][9][10].…”

“…2023, 3, FOR PEER REVIEW 2 of guest molecules that are less polar than water through non-covalent interactions, forming what is known as an inclusion complex. These complexes offer protection to the guest molecules from various chemical and reactive species that could otherwise cause their degradation [7][8][9][10]. As the industrial demand for CDs continues to grow, their production has increased year after year, with significant efforts focused on achieving cost-effective production methods [11].…”