INVESTIGATION INTO THE YELLOWING ON AGING OF SABRIL(R) TABLET CORES

Uncoated Sabril(R) tablet cores under long term storage become slightl y discolored from the initial white to a yellowish off-white color. In order to ensure the aesthetics of the product, Sabril(R) tablet cores are film coated with an opaque white coating. The nature of this yell owing reaction was of interest even though discolored tablets showed n o significant loss of potency on assay. Excipient compatibility studie s showed that the vigabatrin active in Sabril(R) mixed with Avicel(R) (microcrystalline cellulose) in the presence of moisture also became o ff-colored when stressed at elevated temperatures. The nature of the d iscoloration in aged Sabril(R) core tablets was investigated. Chromato graphic and spectroscopic data indicate that the source of this color comes from the Maillard Reaction between vigabatrin and Avicel(R) whic h results in a multitude of products analogous to ''browning reactions '' of food products. A gravimetric determination of the leached colore d products from 7 year old Sabril(R) core tablets gave a residue of le ss than 0.1% relative to vigabatrin. Furthermore, based on spectroscop y, most of this residue was found to be povidone, an excipient in the tablets which was isolated along with the colored substances. Therefor e, the colored products identified in the core of Sabril(R) tablets st ored for an extended period of time represent only minor impurities. T heir formation through aging arises via the Maillard Reaction and woul d only constitute a matter of aesthetics. The latter problem is avoide d by the currently employed film coating process. Similar reactions co uld be predicted for other drugs having amine functional groups if the y are formulated with microcrystalline cellulose or reducing sugars.