(T1530-02-14) Application of Novel Supercritical Fluid Technology in Developing Albendazole Solid Dispersion

Purpose: The purpose of this research is to prepare the amorphous solid dispersion using supercritical fluid technology (SCF) to enhance the solubility and dissolution rate of albendazole.

Methods: An array of hydrophilic polymers with diverse chemical backbone including Kollidon VA64, Soluplus, Eudragit EPO, HPMC-AS, PVA and PVP K30 were screened. The miscibility studies were also conducted by DSC depression method. The most suitable polymer was selected to prepare solid dispersion with ABZ at different drug:polymer ratio, temperatures, pressures, and reaction time. The optimized ABZ solid dispersion was characterized using DSC, XRD and SEM. Dissolution study was carried out using USP dissolution apparatus I at pH 1.2 and 6.8.

Results: Eudragit EPO and PVA were miscible with ABZ according to melting point depression method but did not result in soluble extrudates when prepared using SCF. HPMC-AS did not formed a coherent solid matrix with ABZ. Kollidon VA64 was selected as the polymeric carrier for ABZ for further study due to the porous structure of the final product, which resulted in better drug solubility and release. 80°C, 1500 psi and 2h reaction time was the optimized condition for SCF to prepare ABZ solid dispersion. The ABZ/VA64 solid dispersion showed around 85% drug release vs. 2% for pure ABZ at pH 1.2 and > 7% drug release vs. negligible release of pure ABZ at pH 6.8.

Conclusion: The solid dispersion made by SCF technology can successfully improve the dissolution rate of ABZ at both acid and weakly basic environment. SCF can serve as solvent free, quick and reliable method as surrogate material sparing technique for the preparation of ASD.

Dissolution profile of pure ABZ, ABZ physical mixture and ABZ SCF products at pH 6.8.

DSC scans of pure ABZ and ABZ SCF products.

XRD patterns of pure ABZ and ABZ SCF products.