Solid State Characterization of Domperidone: Hydroxypropyl-β-Cyclodextrin Inclusion Complex.

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Physical Chemistry

Background:

• Domperidone exhibits poor aqueous solubility, limiting its therapeutic efficacy.
• Cyclodextrins, particularly hydroxylpropyl-β-cyclodextrin, are effective complexing agents for improving drug solubility.
• Enhancing domperidone's solubility and dissolution is crucial for optimizing its oral bioavailability.

Purpose of the Study:

• To prepare and characterize an inclusion complex of domperidone with hydroxylpropyl-β-cyclodextrin.
• To evaluate the impact of complexation on domperidone's solubility and dissolution rate.
• To compare the efficacy of ultrasonication and kneading methods for complex preparation.

Main Methods:

• Phase-solubility studies were conducted to determine the effect of hydroxylpropyl-β-cyclodextrin concentration on domperidone solubility.
• Domperidone/hydroxylpropyl-β-cyclodextrin inclusion complexes were prepared using ultrasonication and kneading methods at a 1:1 molar ratio.
• Characterization of the solid-state inclusion complex was performed using FTIR, powder X-ray diffraction (PXRD), and differential scanning calorimetry (DSC).

Main Results:

• Aqueous solubility of domperidone increased with increasing hydroxylpropyl-β-cyclodextrin concentration, following an AL-type phase-solubility diagram.
• FTIR confirmed the structural integrity of domperidone within the complex.
• PXRD indicated that the complex formed was amorphous, while DSC provided further solid-state characterization.
• Solubility studies demonstrated enhanced domperidone solubility in both 0.1M HCl and distilled water upon complexation.
• Ultrasonication proved to be an efficient method for preparing the inclusion complex, as confirmed by drug content analysis.
• Dissolution studies revealed a 1.4-fold increase in the dissolution rate of domperidone from the ultrasonication-prepared complex compared to the pure drug.

Conclusions:

• Complexation with hydroxylpropyl-β-cyclodextrin significantly improves the aqueous solubility and dissolution rate of domperidone.
• The ultrasonication method is effective for preparing domperidone-hydroxylpropyl-β-cyclodextrin inclusion complexes with enhanced drug release.
• The developed inclusion complex holds potential for improving the pharmacokinetic profile and therapeutic effectiveness of domperidone.