Effect of drug-carrier interaction on the dissolution behavior of solid dispersion tablets

Abstract

The objective of this study was to compare the dissolution behavior of tablets prepared from solid dispersions with and without drug-carrier interactions. Diazepam and nifedipine were used as model drugs. Two types of carriers were used; polyvinylpyrrolidone (PVP K12, K30 and K60) and saccharides (inulin 1.8 kDa, 4 kDa and 6.5 kDa). Solid dispersions with various drug loads were prepared by lyophilization. It was found that the drug solubility in aqueous PVP solutions was significantly increased indicating the presence of drug-carrier interaction while the drug solubility was not affected by the saccharides indicating absence of drug-carrier interaction. X-ray powder diffraction and modulated differential scanning calorimetry revealed that all solid dispersions were fully amorphous. Dissolution behavior of solid dispersion tablets based on either the PVPs or saccharides was governed by both dissolution of the carrier and drug load. It was shown that a fast drug dissolution of solid dispersions with a high drug load could be obtained with carrier that showed interaction with the drug.

Keywords::

• Lyophilization
• amorphous solid dispersions
• dissolution
• lipophilic drugs
• polyvinylpyrrolidone
• inulin

Acknowledgements

This research was performed within the framework of project T5-105 of the Dutch Top Institute Pharma. The authors would like to thank P. Pfaffenbach (Solvay Infra Bad Hönningen GmbH, Hannover, Germany) for his assistance on XRPD analysis and the Government Pharmaceutical Organization (Thailand) for the scholarship of P. Srinarong.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.