Study of the Complexation Behavior of Tenoxicam with Cyclodextrins in Solution: Improved Solubility and Percutaneous Permeability

ABSTRACT

Complexation of tenoxicam (TEN) with γ-, HPγ-, β-, HPβ-, and Mβ-cyclodextrin (CD) in aqueous solution at pH 7.4 has been investigated using phase solubility diagrams. TEN formed soluble complexes with 1:1 stoichiometry with all the CDs studied, although the inclusion stability constants (K_1:1) obtained had low values. The presence of propylene glycol (PG) in the dissolution medium decreased the stability constants and led to a higher fraction of free drug by competitive displacement and by an increase in the lipophility of the media.

Among the CDs tested, MβCD was chosen for further studies since TEN–MβCD complexes yielded the best results: good solubility and the highest stability constant. The effect of MβCD and PG on the TEN partitioning coefficient was also studied in skin–buffer systems. Although each substance reduced the partitioning value, the combination of PG and MβCD increased this parameter.

The noticeable increase in solubility of the drug found in the presence of MβCD allowed the formulation of carbopol gels with higher doses of TEN and a reduced amount of cosolvent. The presence of MβCD improved the percutaneous penetration of TEN through abdominal rat skin by increasing the solubility of the drug in the vehicle and by affecting the partitioning behavior of TEN in the skin. In addition, TEN retention in the skin was found to be related to the flux values attained with the corresponding gels.

Key Words:

• Cyclodextrins
• Partitioning coefficient
• Percutaneous penetration
• Skin retention
• Stability constant
• Tenoxicam