Development and evaluation of age-appropriate film-coated tablets of levamisole for paediatric use (2 – 18 years)

Abstract

Objectives: To develop an oral solid dosage form of levamisole suitable for the paediatric population in terms of dose accuracy, palatability, stability and ease of administration.

Methods: Small undividable tablets (Ø5 – 8 mm) in four different strengths were manufactured to allow for flexible and accurate dosing. In vitro dissolution testing was used to determine drug release in different media. The bitter taste of levamisole was masked using a film-coat and assessed in healthy volunteers. Suitability and acceptability of the tablets were evaluated in 100 patients with nephrotic syndrome aged 2 – 18 years participating in a double blind, placebo-controlled, randomised trial.

Results: All tablet strengths showed good taste-masking characteristics and similar, pH independent, dissolution profiles. Successful taste masking was achieved without affecting the dissolution rate. In a total of 100 paediatric patients, more than 20,000 levamisole tablets were swallowed without any difficulties, choking or aspiration.

Conclusion: The formulated tablets were found to be suitable for children aged 2 – 18 years and to provide good dose accuracy.

Keywords::

• film-coated tablets
• levamisole
• nephrotic syndrome
• paediatric formulation
• suitability

Acknowledgements

The authors would like to thank PJ de Vries, MD, PhD for writing and editing assistance and the people of the laboratory of ACE Pharmaceuticals BV, for performing all analytical work and the study investigators for conducting the trial.

Declaration of interest

The double blind, placebo-controlled, randomised, multi-centre levamisole trial was funded by the Dutch Kidney Foundation. The development of levamisole tablets was performed by ACE Pharmaceuticals BV, Zeewolde, the Netherlands. AKV is PhD fellow, employed by ACE Pharmaceuticals BV. MM, KW and CvV are full-time employees of ACE Pharmaceuticals BV.