Improved Delivery through Biological Membranes XXXI: Solubilization and Stabilization of an Estradiol Chemical Delivery System by Modified β‐Cyclodextrins

“All in the Mind”? Brain-Targeting Chemical Delivery System of 17β-Estradiol (Estredox) Produces Significant Uterotrophic Side Effect

“…Solvents used for LC-MS/MS measurements were of HPLC grade and ordered from Fisher Scientific (Atlanta, GA). E2-CDS and Estredox were prepared according to straightforward published methods [13,31,32]. Extreme care was taken for the purification of the chemically stable pyridinium precursor (“oxidized CDS”) and the E2-CDS itself by RP-HPLC [33] to ensure lack of E2 contamination.…”

Targeting drugs to the brain by redox chemical delivery systems

“…139 (The latter observations indicate that 26 may improve cholinergic functions and, thus, may have potential use in the treatment of Alzheimer's disease.). Preclinical development of 27 including formulation with a parenterally safe excipient 2-hydroxypropyl-b-cyclodextrin (HPCD) that forms inclusion complexes with lipophilic drugs 140 and preclinical safety studies have been completed. The ®rst human examination of 27 in a rising dose safety study 141±143 in healthy, postmenopausal women showed a clinically meaningful decrease of serum LH level through a brain-mediated mechanism.…”

Retrometabolism‐Based Drug Design and Targeting

“…The stability of E 2 -CDS was also significantly increased allowing formulation in acceptable form. The rate of ferricyanide-mediated oxidation, a good indicator of oxidative stability, was decreased approximately 10-fold, and shelf life was increased approximately 4-fold, as indicated by t 90 and t 50 values (the time required for 10% and 50% of the active principle to degrade) in a temperature range of C [598]. Similarly promising results were obtained for other CDSs as well; for example, testosterone-CDS [455], lomustine-CDS [520], and benzylpenicillin-CDS [603].…”

“…The corresponding inclusion complex with 2-hydroxypropyl-b-cyclodextrin (HPbCD) solved the formulation problems of E 2 -CDS [598]. This modified cyclodextrin was selected based on its low toxicity observed using various administration routes and based on the fact that alkylation or hydroxyalkylation of the glucose oligomer can disrupt hydrogen bonding and provide increased Figure 54.…”