Investigation of hydroxypropyl-β-cyclodextrin inclusion complexation of two poorly soluble model drugs and their taste-sensatio

The goal for any formulation design of poorly soluble drugs is to increase the solubility. However, increased solubility is a challenge when the drug is administered to the oral cavity as rapidly dispersing or mucoadhesive buccal films. Most drugs are bitter and increased solubility may correlate with perceived worsening of the taste profile.

The aim of the present work was to investigate the dual effect of inclusion complex formation, namely solubilization of two lipophilic model drugs (indomethacin and furosemide) in the hydrophobic cavity of hydroxypropyl-β-cyclodextrin with the aim of increasing the solubility in different electrolyte solutions, and at the same time hinder the taste sensation of the solubilized drug. Taste perception investigations were performed using an electronic tongue on simple solutions, inclusion complexes and on multi-component formulations such as orodispersible films and buccal films. The electrolyte media was found to have an effect on solubilization, association constant and complexation efficiency of both model drugs.

Buffers containing phosphate ions were generally better than other electrolyte media with respect to the solubility parameters, and freeze-drying had a favorable effect on all the desirable properties. This work demonstrated that freeze-dried drug-hydropxypropyl-β-cyclodextrin complexes in solution, or added to orodispersible or buccal film, exhibit different taste sensation as compared to the plain drug in solution or reference films without complexes, indicating a successful taste-masking.

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Article Information: Julia F. Alopaeus, Anja Göbel, Jörg Breitkreutz, Sverre Arne Sande, Ingunn Tho. Journal of Drug Delivery Science and Technology, 2020. https://doi.org/10.1016/j.jddst.2020.102245.

Materials: All salts for buffer preparations were from Sigma Aldrich (St. Louis, MO, USA). HPβCD (Cavasol® W7 HP Pharma) was purchased from Wacker Chemie (Munich, Germany), IMC was from Sigma-Aldrich (St. Louis, MO, USA) and FM was from Fagron (Copenhagen, Denmark). Water was purified with a Milli-Q integrated water purification system for ultrapure water (Merck Millipore, Darmstadt, Germany), and is referred to as Milli-Q water, or in some cases, in-lab distilled water obtained by reverse osmosis was used, and is referred to as demineralized water. Lycoat® RS720 was kindly gifted from Roquette Pharma (Lestrem, France) and glycerol was purchased from Apoteksproduksjon AS (Oslo, Norway). Quinine hydrochloride was purchased from Caesar & Loretz (Hilden, Germany). Potassium chloride (KCl) was acquired from Grüssing (Filsum, Germany). Tartaric acid was purchased from Sigma–Aldrich Laborchemikalien (Schnelldorf, Germany). The saturated silver chloride (AgCl) inner solution for sensors and reference electrodes in the electronic tongue, consisting of 3.33 M KCl in saturated AgCl solution, was provided by Insent (Intelligent Sensor Technology, Kanagawa, Japan). All chemicals used were of analytical grade.