Development and optimization of taste-masked orally disintegrating tablets (ODTs) of clindamycin hydrochloride

Abstract

The purpose of this research was to develop an orally disintegrating tablet (ODT) dosage form containing taste-masked beads of clindamycin HCl. Several formulation strategies were evaluated and a taste-masked ODT of clindamycin HCl was prepared without the use of a waxy cushioning agent. Clindamycin HCl (ca. 46% w/w) was coated onto microcrystalline cellulose beads (Cellets® 200) followed by the addition of a taste-masking layer of amino methacrylate copolymer, NF (Eudragit EPO® (EPO)) coating suspension. The efficiency of both the drug coating process and the taste-masking polymer coating process, as well as the taste masking ODTs was determined using potency and drug release analysis. Magnesium stearate was found to be advantageous over talc in improving the efficiency of the EPO coating suspension. A response surface methodology using a Box–Behnken design for the tablets revealed compression force and levels of both disintegrant and talc to be the main factors influencing the ODT properties. Blending of talc to the EPO-coated beads was found to be the most critical factor in ensuring that ODTs disintegrate within 30 s. The optimized ODTs formulation also showed negligible (<0.5%) drug release in 1 min using phosphate buffer, pH 6.8 (which is analogous to the residence time and pH in the oral cavity). By carefully adjusting the levels of coating polymers, the amounts of disintegrant and talc, as well as the compression force, robust ODTs can be obtained to improve pediatric and geriatric patient compliance for clindamycin oral dosage forms.

• Clindamycin
• coating
• microcrystalline beads
• orally disintegrating tablets
• pediatrics
• taste masking

Acknowledgements

Acknowledgement is given to Dr. Xiaoming Xu for his assistance with the graphical depiction of the beads.

Declaration of interest

The authors’ declare that they have no conflict of interest related to this manuscript.

Part of this research was supported by an FDA-NIH inter-agency agreement and by a Medical Countermeasures Initiative (MCMi) grant. This project was also supported, in part, by an appointment to the ORISE Research Participation Program at CDER administered by the Oak Ridge Institute for Science and Education through an agreement between the U.S. Department of Energy and CDER.

The findings and conclusions in this article have not been formally disseminated by the Food and Drug Administration and should not be construed to represent any Agency determination or policy.