Development and optimization of dextromethorphan hydrobromide oral disintegrating tablets: effect of formulation and process variables

Abstract

Orally disintegrating tablets (ODTs), which disintegrate rapidly (<1 min) in the mouth and do not require water for administration, have become a very popular dosage form. The study aims to develop a simple and inexpensive method of manufacturing ODTs of a sparingly water-soluble drug, Dextromethorphan hydrobromide. Two factors, three levels (3²) full factorial design was used to optimize the diluent, microcrystalline cellulose (X₁) and superdisintegrant, croscarmellose sodium (X₂) concentrations. Disintegration time, hardness and T₅₀ values for all the formulations varied from 12.5 to 152.6 s, 3.58 to 4.92 kp and 0.8 to 2.8 min, respectively. The results indicated that the selected variables have a strong influence on disintegration time, hardness and T₅₀ of the ODTs. The manufactured ODTs formula composed of 30% microcrystalline cellulose in combination with 3% croscarmellose sodium was chosen as optimized formula, as it showed the lowest disintegration time (12.5 ± 1.22 s), low T₅₀ (0.8 min.) and hard tablets (4.92 ± 0.28 kp) amongst other tested ODTs formulations. Hardness of DM ODTs was not affected by changing the type of superdisintegrant and lubricant. The disintegration time was significantly (p < 0.05) increased by using sodium starch glycolate instead of croscarmellose sodium.

Keywords::

• Oral disintegrating tablets
• factorial design
• dextromethorphan hydrobromide
• formulation variables
• process variables

Acknowledgments

The authors extend very special thanks go to Professor Dr. Fars Al Anazy, Director, Kayyali Research Chair for Pharmaceutical Industries for providing open access to all facilities in the laboratory and for funding this work. Many thanks also for Mr. Deli Tuencer, JRS Pharma, Germany and Dr. John Tillotson, SPI Pharma, USA, for their generous donation of chemicals. The authors thank Kayyali Chair for Pharmaceutical Industry, King Saud University, Saudi Arabia, for providing the facilities to perform this study.

Declaration of interest

The authors also acknowledge the financial support of SABIC RESEARCH GRANTS PROGRAM with project number (MED-30?47).