Inhibiting Surface Crystallization and Improving Dissolution of Amorphous Loratadine by Dextran Sulfate Nanocoating

Amorphous formulations provide a solution to poor solubility and slow dissolution of many drugs, but fast surface crystallization can negate their advantages. As in the case of many amorphous drugs, loratadine (LTD) shows much faster crystal growth on the free surface than in the bulk, and its surface crystallization can be inhibited by a polymer nanocoating. LTD is a weak base with a pKa of 5.25. Dextran sulfate (DTS), a pharmaceutically acceptable polymer, is deposited on amorphous LTD from coating solution at pH 3.5 at which LTD is positively charged. Zeta potential measurements support the mechanism of nanocoating by electrostatic deposition. DTS nanocoating is as good as gold coating for inhibiting surface crystallization of amorphous LTD and significantly increases its rate of dissolution. The enhanced dissolution is likely a result of improved wetting of amorphous particles by an aqueous medium. These results indicate that fast surface crystallization of amorphous LTD is enabled by high mobility of surface molecules, and an ultrathin nanocoating can immobilize surface molecules and inhibit surface crystallization. This nanocoating technique can be used to stabilize amorphous drugs prone to surface crystallization and improve their dissolution, and DTS is an effective nanocoating material for basic drugs such as LTD.