Beta-cyclodextrin complexes of celecoxib: molecular-modeling, characterization, and dissolution studies

Area of Science:

• Pharmaceutical Sciences
• Physical Chemistry
• Materials Science

Background:

• Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, exhibits poor aqueous solubility and low bioavailability.
• Improving the solubility and dissolution rate of celecoxib is crucial for enhancing its therapeutic efficacy.

Purpose of the Study:

• To investigate the impact of beta-cyclodextrin complexation on the aqueous solubility and dissolution rate of celecoxib.
• To explore the molecular arrangement and characterize the inclusion complexes formed between celecoxib and beta-cyclodextrin.

Main Methods:

• Phase-solubility studies were conducted to determine the interaction between celecoxib and beta-cyclodextrin.
• Inclusion complexes were prepared using freeze-drying, evaporation, and kneading methods.
• Complexes were characterized using differential scanning calorimetry (DSC), powder X-ray diffractometry (PXRD), and scanning electron microscopy (SEM).
• Molecular modeling and structural designing were employed to understand the complex orientation.

Main Results:

• Beta-cyclodextrin significantly increased the aqueous solubility of celecoxib, forming A(L)-type 1:1 stoichiometric inclusion complexes.
• Characterization techniques confirmed the formation of inclusion complexes and provided insights into their structure and morphology.
• In vitro studies demonstrated a marked improvement in celecoxib's solubility and dissolution rate upon complexation.
• Freeze-dried celecoxib-beta-cyclodextrin complexes exhibited a superior dissolution rate compared to those prepared by other methods.

Conclusions:

• Complexation with beta-cyclodextrin is an effective strategy to enhance the solubility and dissolution rate of celecoxib.
• The freeze-drying method yields celecoxib-beta-cyclodextrin complexes with the most favorable dissolution properties.
• These findings suggest potential for improved oral bioavailability of celecoxib through beta-cyclodextrin complexation.