Pharmaceutical Development, GlaxoSmithKline, Inc., Research Triangle Park, North Carolina, USA.
AAPS PharmSciTech. 2010 Mar;11(1):113-9. doi: 10.1208/s12249-009-9358-3. Epub 2010 Jan 12.
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 degrees 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.
美国食品和药物管理局（FDA）于 1996 年 10 月 4 日批准了安非他酮持续释放（SR）100mg 片剂的新药申请。然而，到 1998 年，FDA 基于储存过程中溶解曲线的增加对该药物产品的稳定性表示担忧。年度报告中提交的数据表明，该药物产品无法满足在国际协调委员会 25°C/60%相对湿度的储存条件下 18 个月的有效期。FDA 强制规定有效期为 12 个月，葛兰素威康（GlaxoWellcome）通过将有效期缩短至 9 个月进一步收紧了这一期限。FDA 还要求对安非他酮 SR 100mg 片剂的稳定性问题提出长期解决方案。通过胶体溶液的研究发现，储存过程中溶解速率的增加是由于释放控制聚合物的酸水解引起的。通过减缓初始溶解速率并增加释放控制聚合物与酸稳定剂的比例，该药物产品成功进行了重新配方。新配方使用与原始配方相同的成分和制造单元工艺。该改剂型药物产品于 2000 年 10 月 11 日获得 FDA 批准，有效期为 18 个月。在 2005 年 12 月 1 日向 FDA 的年度更新中，有效期延长至 36 个月。
