A Way to Increase the Bioaccesibility and Photostability of Roflumilast, a COPD Treatment, by Cyclodextrin Monomers

• Main Authors: Adrián Matencio, Samanta Hernández-García, Francisco García-Carmona, José Manuel López-Nicolás
• Format: Article
• Language: English
• Published: MDPI AG 2019-05-01
• Series: Polymers
• Subjects: roflumilast; cyclodextrins; digestion; fluorescence; phosphodiesterase
• Online Access: https://www.mdpi.com/2073-4360/11/5/801

Roflumilast is an orally available inhibitor of phosphodiesterase (PDE) type 4, which is widely used in chronic obstructive pulmonary diseases. However, it has low solubility and adverse effects include diarrhea and nausea. Since its solubilization may improve treatment and, dismissing any adverse effects, its interaction with cyclodextrins (CDs) was studied. The Higuchi-Connors method was used to determine the complexation constant with different CDs, pH values and temperatures. Molecular docking was used to predict interaction between the complexes. An in vitro digestion experiment was carried out to test roflumilast protection. Finally, the photostability of the complex was evaluated. The complex formed with &#946;-CD had the highest <i>K</i>₁₁ value (646 &#177; 34 M^&#8722;1), although this value decreased with increasing temperature. Similarly, <i>K</i>₁₁ decreased as the pH increased. In vitro digestion showed that CDs protect the drug during digestion and even improve its bioaccessibility. Finally, CDs reduced the drug&#8217;s extreme photosensitivity, originating a fluorescence signal, which is described for first time. The kinetic parameters of the reaction were obtained. This study not only completes the complexation study of roflumilast-CD, but also points to the need to protect roflumilast from light, suggesting that tablets containing the drug might be reformulated.