The Food and Drug Administration (FDA) approved the New Drug Application for Wellbutrin sustained release (SR) 100 mg tablets on October 4, 1996. However, by 1998, the FDA expressed concern about the stability of this drug product based on an increase in the dissolution profile on storage. Data submitted in the annual report showed that this drug product could not meet the expiry of 18 months at the International Committee on Harmonization storage condition of 25°C/60% relative humidity. The FDA mandated a 12-month expiry and GlaxoWellcome tightened this further by instituting an expiry of 9 months. The FDA also requested a long-term solution to the stability of Wellbutrin SR 100 mg tablets. Investigations via colloidal solutions revealed that the dissolution rate increase on storage occurred due to acid hydrolysis of the release controlling polymer. This drug product was successfully reformulated by slowing the initial dissolution rate and having an increased ratio of release controlling polymer to acid stabilizer. The reformulation used the same ingredients and manufacturing unit processes as the original formulation. The reformulated drug product was approved by the FDA on October 11, 2000 with an 18-month shelf-life. The shelf-life was extended to 36 months in an annual update to the FDA on December 1, 2005.
展开▼
机译:美国食品药品监督管理局(FDA)于1996年10月4日批准了100毫克维特布林缓释(SR)新药申请。但是,到1998年,FDA对这种药物产品的稳定性表示关注,原因是这种药物的使用量增加了。储存时的溶出曲线。年度报告中提交的数据表明,该药品不能满足国际协调委员会在25°C / 60%相对湿度的条件下18个月的有效期。 FDA规定了12个月的有效期,而葛兰素威尔康通过设置9个月的有效期进一步收紧了这一期限。 FDA还要求长期解决Wellbutrin SR 100 mg片剂的稳定性问题。通过胶体溶液的研究表明,由于释放控制聚合物的酸水解,导致储存时溶解速率增加。通过减慢初始溶解速度并提高了控释聚合物与酸稳定剂的比例,成功地重新配制了该药物产品。重新配方使用与原始配方相同的成分和制造单元工艺。重新配制的药物产品于2000年10月11日获得FDA批准,保质期为18个月。在2005年12月1日向FDA进行的年度更新中,保质期延长至36个月。
展开▼