Controlled release of highly soluble BCS Class I drugs

Metoclopramide is a highly soluble (> 200 mg/ml), highly absorbable (BA > 80%) drug (BCS Class I), used to treat GI disorders, and as antiemetic in chemotherapy treatments. Very bitter taste. It is usually administered 3 to 4 times a day.
Controlled release formulations would maintain constant drug concentration in plasma, reduce drug dosing frequency while prolonging the antiemetic effect.

Applying Variosol technology, it was possible to:

  • formulate microspheres within excipient blends which can solubilize the drug and modulate its release
  • encapsulate drug in lipidic matrix microspheres, forming a physical barrier between the drug and the taste receptors on the tongue
  • modulate metoclopramide release by modifying the excipients composition without significantly changing the processing conditions

Metoclopramide (MCP) dissolution profile in PBS at PH 6.8 (small intestinal pH), from different microspheres formulations based on Variosol technology. Drug release rate can be modified by selection of excipients and minimal adjustments of process conditions.
L. Segale et al., CRS Newsletter, 25, 3, (2008), pp.16-17.

Controlled release microspheres maintain their matrix structure during drug release process.

Electron Microscopy (SEM) images of MCP-CeCo50 microparticles before drug release test in PBS pH 6.8.

SEM images of MCP-CeCo50 microparticles collected after drug release test in PBS pH 6.8.