Chitosan–kaolin coprecipitate as disintegrant in microcrystalline cellulose-based pellets elaborated by extrusion–spheronization

Abstract

The usefulness of a coprecipitate of chitosan and kaolin as disintegrant in the pellets of microcrystalline cellulose (MCC) and hydrochlorothiazide (HCT) (as a model of poorly water-soluble drug) produced by extrusion–spheronization was evaluated in this study. The effectiveness of chitosan–kaolin coprecipitate to increase the dissolution rate was compared with that of kaolin and chitosan. A possible synergy effect was also evaluated between the coprecipitate, kaolin or chitosan and sorbitol, added to the pellets as a very water-soluble diluent. The chitosan–kaolin coprecipitate, the kaolin or the chitosan allowed pellets to be obtained of adequate size, roundness, mechanical strength and flow properties. Furthermore, the incorporation of chitosan–kaolin coprecipitate or chitosan significantly increased the dissolution rate of HCT independently of the sorbitol content. The effects on the dissolution of HCT derived from the incorporation of coprecipitate to the pellets can be attributed to its content of chitosan. However, the addition of kaolin into the pellets did not significantly affect the HCT dissolution process. The pellets incorporating coprecipitated chitosan–kaolin or chitosan and the maximum proportion of sorbitol (50%) led to the highest HCT dissolution rate and experienced a rapid and complete disintegration in the dissolution medium.

Keywords::

• Pellet
• extrusion–spheronization
• disintegrant
• chitosan
• kaolin
• microcrystalline cellulose

Acknowledgments

The authors would like to thank Roquette Laisa España, S.A. (Spain) for the generous gift of samples of sorbitol.

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 this paper.