Aripiprazole-cyclodextrin binary systems for dissolution enhancement: effect of preparation technique, cyclodextrin...

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Physical Chemistry

Background:

• Aripiprazole, an antipsychotic, exhibits poor aqueous solubility, limiting its therapeutic efficacy.
• Cyclodextrins (CDs) are widely used to improve the solubility and bioavailability of poorly soluble drugs.
• Both natural β-cyclodextrin (β-CD) and chemically modified hydroxypropyl-β-cyclodextrin (HP-β-CD) were investigated.

Purpose of the Study:

• To evaluate the impact of β-CD and HP-β-CD on aripiprazole's solubility and dissolution rate.
• To compare different preparation techniques (kneading, microwave irradiation, freeze-drying) for aripiprazole-CD binary systems.
• To determine the optimal drug-to-CD molar ratio (1:1 and 1:2) for enhanced drug performance.

Main Methods:

• Phase solubility studies were conducted to assess drug-excipient interactions and complexation efficiency.
• Solid binary systems were prepared using kneading, microwave irradiation, and freeze-drying methods.
• Dissolution studies were performed on the prepared systems and physical mixtures for comparison.

Main Results:

• Phase solubility indicated higher-order complex formation with greater complexation efficiency for HP-β-CD compared to β-CD.
• Aripiprazole dissolution rate increased with higher CD molar ratios and was significantly influenced by CD type and preparation method.
• The freeze-drying technique, particularly with HP-β-CD at a 1:2 molar ratio, demonstrated superior performance in enhancing drug dissolution.

Conclusions:

• The freeze-dried system of aripiprazole with HP-β-CD at a 1:2 molar ratio is an effective strategy for improving aripiprazole dissolution.
• This approach holds potential for enhancing the oral bioavailability of aripiprazole.
• Optimizing cyclodextrin complexation and preparation methods is crucial for poorly soluble drugs.