Effect of Cyclodextrin Types and Co-Solvent on Solubility of a Poorly Water Soluble Drug

Abstract

The aim of the study was to investigate the solubility of piroxicam (Prx) depending on the inclusion complexation with various cyclodextrins (CDs) and on ethanol as a co-solvent. The phase-solubility method was applied to determine drug solubility in binary and ternary systems. The results showed that in systems consisting of the drug dissolved in ethanol–water mixtures, the drug solubility increased exponentially with a rising concentration of ethanol. The phase solubility measurements of the drug in aqueous solutions of CDs, β-CD and γ-CD exhibited diagrams of AL-type, whereas 2,6-dimethyl-β-CD revealed AP-type. The destabilizing effect of ethanol as a co-solvent was observed for all complexes regardless of the CD type, as a consequence of it the lowering of the complex formation constants. In systems with a higher concentration of ethanol, the drug solubility was increased in opposition to the decreasing complex formation constants. According to this study, the type of CDs played a more important role on the solubility of Prx, and the use of ethanol as a co-solvent exhibited no synergistic effect on the improvement of Prx solubility. The Prx solubility was increased again due to the better solubility in ethanol.

Anticancer activity of the supercritical extract of Brazilian green propolis and its active component, artepillin�C: Bioinformatics and experimental analyses of its mechanisms of action

“…However, due to their poor solubility in aqueous solvents, their use is limited in in vitro and in vivo studies. Cyclodextrins (CDs), with inner lipophilic cavities and hydrophilic outer surfaces, are capable of encapsulating molecules by non-covalent inclusion (47,48). We previously used γCD to conjugate with CAPE to generate a CAPE-γCD complex that showed significant anticancer activity (12).…”

Immediate Release Formulation of Inhaled Beclomethasone Dipropionate-Hydroxypropyl-Beta-Cyclodextrin Composite Particles Produced Using Supercritical Assisted Atomization

“…As the environment becomes more hydrophobic, the guest (BDP) tends to dissolve in the surrounding medium or dissolve in the medium as a CD/BDP complex. This phenomenon has been reported in many studies, regardless of the type of CD, and destabilization of ethanol as a co-solvent has been observed [ 32 , 33 ].…”

Elucidating the Structure-Function Relationship of Solvent and Cross-Linker on Affinity-Based Release from Cyclodextrin Hydrogels

“…Ethanol is capable of weakly associating with the CD pocket; however, Autodock simulations calculated significantly lower binding energies for ethanol than MNC (−1.6, −1.7 and −1.5 kcal/mol for pCD-α, -β and -γ, respectively), so any ethanol occupying the pocket would be displaced by minocycline. We hypothesize that ethanol is tilting the thermodynamic equilibrium away from MNC-CD association by decreasing the energetic favorability of desolvating MNC by associating into the CD pocket [21,22].…”