Comparison of Aqueous and 1-Octanol Solubility as well as Liquid–Liquid Distribution of Acyclovir Derivatives and Their Complexes with Hydroxypropyl-β-Cyclodextrin

Abstract

The aim of the presented work is the comparison of aqueous and 1-octanol solubilities of different acyclovir derivatives and their hydroxypropyl-β-cyclodextrin inclusion complexes. The solubility measurements were carried out at different temperatures over the range 25–45 °C using water, 1-octanol, water saturated with 1-octanol, 1-octanol saturated with water, buffered aqueous solutions (pH = 5.5 and 7.0) and buffered aqueous solutions containing cyclodextrin as solvents. The aqueous solubilities of the compounds are very low but may be enhanced by complexation with hydroxypropyl-β-cyclodextrin, especially if the acyclovir derivatives have aromatic groups which may be included in the cyclodextrin cavity. The values of 1-octanol–water partition coefficients of acyclovir derivatives, obtained using extraction experiments, showed a similar sequence as the solubility results in 1-octanol. Additionally, some molecular mechanics and molecular dynamic calculations were performed to determine optimized structures of acyclovir derivative complexes with β-cyclodextrin treated as a model.

Enhanced oral bioavailability of acyclovir by inclusion complex using hydroxypropyl-β-cyclodextrin

“…Thus, disappearance of thermal features of drug ascertained the formation of true complex of drug-HP-b-cyclodextrin, wherein the drug molecules penetrated into the cyclodextrin cavity by replacing the water molecules. The possible mechanism of the complex formation between acyclovir and HP-b-cyclodextrin was reported in the literature (Świerzewski et al, 2002;Zielenkiewicz et al, 2010;Koźbiał & Gierycz, 2013). The authors suggest that the complexation of acyclovir by HP-b-cyclodextrin is likely due to the interaction/association between the hydroxyl ethoxy methyl group of acyclovir with the hydrophobic cavity of cyclodextrin.…”

“…Among the cyclodextrin derivatives, hydroxypropyl-b-cyclodextrin (HP-b-cyclodextrin) is most widely investigated for drug complexation and has captivated the drug delivery scientists probably owing to its high aqueous solubility, better complexation ability, greater stability, non-toxicity and its potential to enhance oral bioavailability of low aqueous soluble drugs (Irie & Uekama, 1997;Nasongkla et al, 2003). Recently, one attempt has been reported to enhance the aqueous solubility of acyclovir by preparing inclusion complex using HP-b-cyclodextrin (Koźbiał & Gierycz, 2013). The objective of this study was to carry out a systematic investigation on the effect of inclusion complex of acyclovir using HPb-cyclodextrin in enhancing the oral bioavailability.…”

Isothermal titration calorimetry (ITC) study of natural cyclodextrins inclusion complexes with tropane alkaloids

“…The CDs inclusion complexes affect many physicochemical properties of their quests, such as aqueous solubility and rate of dissolution. The successful enhancing of the solubility of poorly water-soluble drugs belongs to the most important application of such complexes [3][4][5][6].…”

The Lord of the NanoRings: Cyclodextrins and the battle against SARS-CoV-2

“…In this conformation, all the secondary hydroxyl groups (attached to the C2 and C3 carbon atoms of the glucose units) are oriented toward the wide edge of the cavity (known as the head of the CD structure), whereas the primary hydroxyls form the narrow entry of the cavity. Such distribution of polar groups determines the specific physicochemical properties of these molecules, including their solubility and their ability to encapsulate hydrophobic groups in their cavity (Koźbiał and Gierycz, 2013). As a result, CDs are widely used to increase the solubility, to protect or to reduce the toxicity of a large variety of different molecules including drugs, dyes and surfactant agents.…”