Abstract

DEXTROMETHORPHAN HYDROBROMIDE EXTENDED-RELEASE TABLETS PREPARED BY HIGH SHEAR WET GRANULATION

Gamal M. Mahrous*, Sayed H. Auda, Ahmed S. Alenazi, Lubna Y. Ashri and Amal El Sayeh F. Abou El Ela

.

Abstract

The present study aimed to investigate the effect of wet granulation using a high shear mixer on dextromethorphan (DM) produced granules properties. The effect of Carbopol 71G-NF, HPMC K15M and CMC on DM release from the prepared granules after tableting was also studied. DSC showed that the drug endothermic peak was seen in its melting range with the corresponding physical mixtures indicating no interaction between DM and the tested excipients. This was also confirmed by FTIR results. The angle of repose for all granule mesh cuts ranged from 31.6° to 33.5° indicating good flowability, which was confirmed by the results of Carr’s index and Hausner ratio. The average content for all granule sizes ranged between 98.5 to 108% of the theoretical content implying good content uniformity. DM release from tablet formulations in phosphate buffer pH 6.8 revealed that formula F1, which is compressed granules with no polymer added, showed immediate release. The addition of 20 % Carbopol resulted in extended release tablets that approaches nearly zero order release kinetics. Using a combination of Carbopol 10% and CMC 10% showed anomalous nonfickian release pattern with more extended release. However, a combination of Carbopol with HPMC lead to more sustained release that is controlled with Higuhci diffusion model. Repeating the release experiments in biphasic media (pH 1.2 for 2 h then in pH 6.8 for up to 24 h) showed extended release behavior with an increase in the release rate constant for all formulations.

Keywords: .