“Back to the Future”: A New Look at Hydroxypropyl Beta-Cyclodextrins

Abstract

Since the discovery about 30 years ago (2-hydroxypropyl) beta-cyclodextrin, a highly soluble derivative of beta-cyclodextrin, has become an approved excipient of drug formulations included both in the United States and European Pharmacopoeias. It is recommended to use as solubilizer and stabilizer for oral and parenteral formulations. Recently, its pharmacological activity has been recognized in various diseases. The increasing applications require a closer look to the structure-activity relationship. As (2-hydroxypropyl) beta-cyclodextrin (HPBCD) is always a mixture of isomers with various degrees and pattern of hydroxypropylation, no wonder that the products of different manufacturers are often different. Several HPBCDs were compared applying a battery of analytical tools including thin layer chromatography, high performance liquid chromatography (HPLC), HPLC-mass spectrometry (MS), and matrix-assisted laser desorption MS. We studied how the average degree of substitution affects the aggregation behavior, the toxicity, and the solubilizing effect on poorly soluble drugs. We found that the products with low average degree of substitution are more prone to aggregation. The samples studied are nontoxic to Caco-2 cells and have low hemolytic activity. The solubility enhancement of poorly soluble drugs decreases or increases with increasing degree of substitution or shows a maximum curve depending on the properties of the guest.

Cyclodextrins as Emerging Therapeutic Tools in the Treatment of Cholesterol-Associated Vascular and Neurodegenerative Diseases

“…This hydroxypropyl derivative of β-CD displays improved water solubility properties enabling to increase solubilization rate, encapsulation and better delivery of lipophilic drugs [99,100]. In the atherosclerosis context, the evaluation of the effect of HPβCD in vitro has been restricted to macrophages and macrophage-derived foam cells, in which HPβCD stimulate their cholesterol efflux [53][54][55].…”

Synthesis and adsorption behavior of hydroxypropyl-β-cyclodextrin–polyurethane magnetic nanoconjugates for crystal and methyl violet dyes removal from aqueous solutions

“…Thereaer, the product was extracted from the insoluble Na 2 SO 4 with ethanol (95%) or isopropyl alcohol (99%), and the extract was evaporated. 27 2.2.3. HPbCD-conjugated magnetic nanoparticles.…”

Cyclodextrins and Iatrogenic Hearing Loss: New Drugs with Significant Risk

“…The main by-products of HPβCD synthesis are unreacted β-cyclodextrin and propylene glycol. The amount of impurities increases with the degree of substitution, as greater amounts of NaOH and propylene oxide are required for the reaction (Malanga et al, 2016 ). A variety of commercial HPβCD products have been examined and proven ototoxic, including formulations from Sigma-Aldrich (C0926, H107; Ward et al, 2010 ; Crumling et al, 2012 ; Cronin et al, 2015 ), Roche (Kleptose HPB; Davidson et al, 2016 ), and a highly characterized and purified form of Kleptose HPB used in the phase 2/3 clinical trials (VTS-270; Davidson et al, 2016 ; Ory et al, 2017 ; Yergey et al, 2017 ).…”