| Development and In Vivo Evaluation of Extended Release Dextromethorphan Tablets Part 1 Satinder S. Bharaj, Sevgi Takka*, Gary R. Kelm, and Adel Sakr Industrial Pharmacy Program, College of Pharmacy, University of Cincinnati, Ohio (USA) Correspondence: Prof. Dr. Adel Sakr, Industrial Pharmacy Program, College of Pharmacy, University of Cincinnati Medical Center, 3223 Eden Avenue, Cincinnati, OH 45267-0004 (USA), Fax 1 (513) 558-72 57, e-mail: Adel.Sakr@Uc.Edu * Current address: University of Gazi, Faculty of Pharmacy, Department of Pharmaceutical Technology, Ankara (Turkey)
The objective of this study was to de-velop 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 random-ized 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 Hustenstiller retardkap-seln) each containing 60 mg DMHBr were given once a day while an immedi-ate 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 Cmax 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 hydroxy-propyl methylcellulose and methacrylic acid copolymer combination and the polyvinylacetate/povidone copolymer ER matrix tablets within 2 h, and the mean Tmax 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).
Key words CAS 6700-34-1 • Dextromethorphan • Extended release tablets • Matrix tablets, in vivo study, in vitro-in vivo correlation |
