Preparation and characterization of simvastatin/hydroxypropyl-beta-cyclodextrin inclusion complex using supercritical...

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Physical Chemistry

Background:

• Simvastatin (SV) is a practically insoluble drug, limiting its bioavailability and therapeutic efficacy.
• Improving the aqueous solubility and dissolution rate of SV is crucial for enhancing its hypolipidemic activity.

Purpose of the Study:

• To prepare and characterize simvastatin (SV) inclusion complexes with hydroxypropyl beta-cyclodextrin (HP-beta-CD) using the supercritical antisolvent (SAS) process.
• To evaluate the impact of complexation on SV's aqueous solubility, dissolution rate, and hypolipidemic activity.

Main Methods:

• Preparation of SV/HP-beta-CD inclusion complexes via the supercritical antisolvent (SAS) process.
• Characterization using phase solubility diagrams, DSC, PXRD, FT-IR, and SEM.
• Assessment of aqueous solubility, dissolution rates, and in vivo hypolipidemic activity.

Main Results:

• The SAS process successfully formed 1:1 stoichiometric SV/HP-beta-CD inclusion complexes with high complexation constants.
• Complexation resulted in an amorphous form of SV, evidenced by DSC and PXRD, and demonstrated intermolecular hydrogen bonding via FT-IR.
• The inclusion complex exhibited significantly enhanced aqueous solubility and dissolution rates compared to pure SV and physical mixtures.
• SV/HP-beta-CD inclusion complexes showed improved hypolipidemic effects in reducing cholesterol and triglyceride levels.

Conclusions:

• The supercritical antisolvent (SAS) process is an effective method for preparing simvastatin (SV)/hydroxypropyl beta-cyclodextrin (HP-beta-CD) inclusion complexes.
• Complexation significantly enhances the solubility, dissolution rate, and hypolipidemic activity of simvastatin.
• This approach offers a promising strategy for improving the oral bioavailability and therapeutic performance of poorly soluble drugs.