Control of drug release by incorporation of sorbitol or mannitol in microcrystalline-cellulose-based pellets prepared by extrusion-spheronization

Abstract

Mixtures of microcrystalline cellulose (MCC) with sorbitol (up to 50%) or mannitol (up to 80%) were investigated as major excipients for controlled accelerated release of the model poorly water-soluble drug hydrochlorothiazide from pellets prepared by extrusion/spheronization. Optimal wetting volume decreased with increasing polyol content and was always less than the volume required for maximum wet mass consistency. All pellet formulations had satisfactory morphological, mechanical and flow properties, although sorbitol/MCC pellets were rougher than mannitol/MCC pellets. Together they presented a wide range of drug release profiles in 0.1 M HCl, allowing the rate of drug release into aqueous media to be controlled by manipulation of sorbitol or mannitol content. Pellets with a 50% sorbitol content released hydrochlorothiazide faster than pellets with a 50% mannitol content because of their greater porosity and the greater solubility of sorbitol in water. Fastest release was from pellets with an 80% mannitol content, which rapidly underwent complete disintegration.

Keywords::

• Extrusion-spheronization
• pellet
• mannitol
• sorbitol
• microcrystalline cellulose

Acknowledgements

We also thank Roquette Laisa España, S.A. (Spain) for the generous gift of samples of mannitol.

Declaration of interest

This work was supported by grant 07CSA006203PR from the CII (Xunta de Galicia). The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.