Tablet splitting: Product quality assessment of metoprolol succinate extended release tablets.
Metoprolol succinate extended release tablets comprise a multiple unit system containing metoprolol succinate in a multitude of controlled release pellets. Each pellet acts as a separate drug delivery unit and is designed to deliver metoprolol continuously over the dosage interval. Despite the flexibility that controlled release pellets may offer, segregation is one of the challenges that commonly occur during tableting for such drug delivery system. Since all commercial metoprolol succinate extended release tablets are scored, they are deemed suitable for splitting. The present study was aimed at utilizing an innovative technology to determine the dose uniformity for split tablets. Four marketed drug products consisting of innovator and generics were evaluated for effect of splitting on weight, assay and content uniformity. Novel analytical tool such as near infrared (NIR) chemical imaging was used to visualize the distribution of metoprolol succinate and functional excipients on the surfaces of the marketed tablets. The non-homogeneous distribution of directly compressed metoprolol succinate beads on the surface of the tablets as well as the split intersection explained the large variation in the split tablets' weight and content uniformity results. The obtained results indicated the usefulness of NIR chemical imaging to determine the need for content uniformity studies for certain split tablets.
Zhao
Na
N
Division of Product Quality Research, Office of Testing and Research, Center for Drug Evaluation and Research (CDER), Food and Drug Administration (FDA), United States.
Zidan
Ahmed
A
Tawakkul
Mobin
M
Sayeed
Vilayat A
VA
Khan
Mansoor
M
D000319:Adrenergic beta-Antagonists / Q000737:chemistry* / Q000592:standards; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D008790:Metoprolol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000592:standards; D011786:Quality Control; D019265:Spectroscopy, Near-Infrared; D013607:Tablets
D000319:Adrenergic beta-Antagonists; D003692:Delayed-Action Preparations; D013607:Tablets; D008790:Metoprolol