Floating matrix dosage form for dextromethorphan hydrobromide based on gas forming technique: In vitro and in vivo evaluation in healthy volunteers

• Published in: European journal of pharmaceutical sciences Vol. 42; no. 1; pp. 99 - 105
• Main Authors: Hu, Liandong, Li, Li, Yang, Xun, Liu, Wei, Yang, Jianxue, Jia, Yanhong, Shang, Chuang, Xu, Hongxin
• Format: Journal Article
• Language: English
• Published: Kindlington Elsevier B.V 18.01.2011; Elsevier
• Subjects: Absorption; Adult; Antitussive Agents - administration & dosage; Antitussive Agents - blood; Antitussive Agents - chemistry; Antitussive Agents - pharmacokinetics; Biological and medical sciences; Biological Availability; Cross-Over Studies; Dextromethorphan - administration & dosage; Dextromethorphan - blood; Dextromethorphan - chemistry; Dextromethorphan - pharmacokinetics; Dextromethorphan hydrobromide; Excipients - chemistry; Floating; General pharmacology; Hardness; Humans; In vitro release; Male; Medical sciences; Orthogonal experiment design; Pharmaceutical technology. Pharmaceutical industry; Pharmacokinetics; Pharmacology. Drug treatments; Solubility; Stomach - metabolism; Sustained release; Tablets, Enteric-Coated; Technology, Pharmaceutical - methods; Tissue Distribution; Young Adult; Sustained release; In vitro release; Dextromethorphan hydrobromide; Orthogonal experiment design; Floating; Pharmacokinetics; Morphinan derivatives; Human; Evaluation; Pharmaceutical technology; Healthy subject; Controlled release form; Opiates; Forming; Antitussive agent; Dextromethorphan; In vitro; Design; In vivo; Dosage form; NMDA receptor; Release; Matrix system
• ISSN: 0928-0987; 1879-0720; 1879-0720
• DOI: 10.1016/j.ejps.2010.10.010

The objective of this study was to develop the dextromethorphan hydrobromide sustained-release (DMB-SR) tablets using floating technique to prolong the gastric residence time and compared their pharmacokinetic behavior with conventional sustained release tablets. DMB-SR floating tablets were prepared employing hydroxypropyl methylcellulose (HPMC) as hydrophilic gel material, sodium bicarbonate as gas-generating agent and hexadecanol as floating assistant agent. An orthogonal experiment design method was used to select the optimized formulation. The floating tablets were evaluated for uniformity of weight, hardness, friability, drug content, floating characteristics, in vitro release and in vivo bioavailability. The optimized tablets were prepared with HPMC K4M 25 mg, sodium bicarbonate 20 mg and hexadecanol 18 mg. The prepared tablets could float within 3 min and maintain for more than 24 h. The data of physical parameters were all lie within the limits. Drug release at 12 h was more than 85%. The comparative pharmacokinetic study was performed by administration of the DMB-SR floating tablets and conventional DMB-SR tablets. The area under curve of plasma concentration–time (AUC) of floating tablets was slightly higher than that of reference tablets, T max was prolonged apparently. The results showed the floating tablets are a feasible approach for the sustained-release preparation of drugs, which have limited absorption sites in the stomach.