Development and in vivo evaluation of extended release dextromethorphan tablets Part 1

The objective of this study was to develop extended release (ER) tablets of dextromethorphan hydrobromide (DMHBr, CAS 6700-34-1). A comparison with a marketed ER product in vivo was made. In vitro drug release data were obtained and the three formulations were found to be similar upon application of the FDA f2 similarity factor. A randomized crossover study was performed in healthy adult male beagle dogs for the in vivo evaluation. The three treatments, 1.) a hydroxypropyl methylcellulose and methacrylic acid copolymer combination ER matrix tablet, 2.) a polyvinylacetate/povidone copolymer ER matrix tablet and 3.) a marketed German ER capsule product (Tuss Hustenstitler retardkapseln) each containing 60 mg DMHBr were given once a day while an immediate release (IR) gelatin capsule containing 30 mg DMHBr was given twice a day. It was found that the AUC((0-inf)) of the commercial ER capsule (243 ng/ml/h) was not statistically different from the control IR capsules (221 ng/ml/h) and the hydroxypropyl methylcellulose and methacrylic acid copolymer combination ER matrix tablet (283 ng/ml/h). AUC((0-inf)) was statistically different from the polyvinylacetate/povidone polymer ER matrix tablet (327 ng/ml/h). The C-max data showed that there was no statistical significant difference between the commercial marketed product and the two extended release formulations. The maximum concentration was reached for the hydroxypropyl methylcellulose and methacrylic acid copolymer combination and the polyvinylacetate/povidone copolymer ER matrix tablets within 2 h, and the mean T-max was found 3.5 h for the commercial marketed product. The in vivo data showed that the two ER tablet formulations were bioequivalent to each other and to the commercial ER capsule after 10 h. The in vitro dissolution testing indicated they had similar dissolution behavior according to the FDA guidelines (f2 factor).