Solubility of Cyclodextrins and Drug/Cyclodextrin Complexes

Abstract

Cyclodextrins (CDs), a group of oligosaccharides formed by glucose units bound together in a ring, show a promising ability to form complexes with drug molecules and improve their physicochemical properties without molecular modifications. The stoichiometry of drug/CD complexes is most frequently 1:1. However, natural CDs have a tendency to self-assemble and form aggregates in aqueous media. CD aggregation can limit their solubility. Through derivative formation, it is possible to enhance their solubility and complexation capacity, but this depends on the type of substituent and degree of substitution. Formation of water-soluble drug/CD complexes can increase drug permeation through biological membranes. To maximize drug permeation the amount of added CD into pharmaceutical preparation has to be optimized. However, solubility of CDs, especially that of natural CDs, is affected by the complex formation. The presence of pharmaceutical excipients, such as water-soluble polymers, preservatives, and surfactants, can influence the solubilizing abilities of CDs, but this depends on the excipients’ physicochemical properties. The competitive CD complexation of drugs and excipients has to be considered during formulation studies.

COVID-19: A Recommendation to Examine the Effect of Mouthrinses with β-Cyclodextrin Combined with Citrox in Preventing Infection and Progression

“…The most usual CDs, called, α, β, and γ, contain 6-, 7-, and 8-glucopyranoside units, respectively. CDs are cyclic oligosaccharides used for improving bioavailability of medicinal products and water-solubility [43]. Also, CDs can be employed to prevent or reduce ocular and gastrointestinal irritation, decrease or eliminate disagreeable tastes or smells, prevent interactions between drugs or drug additives in a formulation [44].…”

Different Approaches for Enhancement of Curcumin Aqueous Solubility and Dissolution rate

“…For instance, after the same time CUR/HPβ-CD solid dispersion exhibited CUR dissolutions of about 95 % (Figure 4). The observed increase in the dissolution rate of CUR could be attributed to the formation of inclusion complexe with HPβ-CD where the drug is being incorporated into the interior CD cavity [16,53]. Dissolution CUR from the physical mixture was faster than the drug alone for CUR/HPβ-CD due to increased drug wettability by this hydrophilic carrier.…”

Improved Dissolution and Pharmacokinetics of Abiraterone through KinetiSol® Enabled Amorphous Solid Dispersions

“…It can form an inclusion complex with poorly water-soluble drugs by interacting with the hydrophobic groups of the drug and including them within its cavity. This interaction improves the drug's physicochemical properties and thus increases the drug's aqueous solubility [54]. Oligomer-based KSD dissolution performance surpassed that of polymer-based KSDs, likely because in addition to abiraterone amorphization in the Lot 5 KSD, HPBCD further enhanced abiraterone solubility by forming inclusion and non-inclusion complexes with abiraterone, likely in KSD and during dissolution [54,55].…”

“…This interaction improves the drug's physicochemical properties and thus increases the drug's aqueous solubility [54]. Oligomer-based KSD dissolution performance surpassed that of polymer-based KSDs, likely because in addition to abiraterone amorphization in the Lot 5 KSD, HPBCD further enhanced abiraterone solubility by forming inclusion and non-inclusion complexes with abiraterone, likely in KSD and during dissolution [54,55]. Moreover, the oligomer HPBCD has a more hydrophilic outer surface than the other polymers studied, thereby leading to higher abiraterone hydration and solubilization.…”