Sue-Chu M, Kristensen S, Tønnesen H H
School of Pharmacy, Department of Pharmaceutics, University of Oslo, Blindern, 0316 Oslo, Norway.
Pharmazie. 2009 Jul;64(7):428-35.
There has been a gradual change in the relative amounts of synthetic and biosynthetic bulk riboflavin (RF) supplied to the overall market over the past years. The two sources of drug substance seem to have different photochemical properties that cannot be readily predicted. Alternating between the two qualities of RF therefore seems to influence the photochemical properties of the final product in a rather unpredictable way. A change in production method introduces the possibility of a change in polymorphic form which may alter the photoreactivity of the substance. The drug substance and tablets become green upon light exposure. The biosynthetic bulk material appears to be less photostable than the synthetic bulk material after inadvertent exposure to radiation or at elevated humidity. The observed color change cannot be explained by the formation of degradation products but is strongly dependent on the humidity level within the drug substance or preparation. The change in color was dramatically increased (by a factor up to 7) when the drug substance was formulated as tablets. Interactions were observed between RF and individual tablet components by mixing and compression at low pressure prior to exposure.
在过去几年中，供应给整个市场的合成和生物合成散装核黄素（RF）的相对数量发生了逐渐变化。这两种原料药来源似乎具有不同的光化学性质，难以轻易预测。因此，在这两种质量的RF之间交替使用似乎会以相当不可预测的方式影响最终产品的光化学性质。生产方法的改变引入了多晶型形式变化的可能性，这可能会改变该物质的光反应性。原料药和片剂在光照下会变绿。在意外暴露于辐射或高湿度环境后，生物合成散装材料似乎比合成散装材料的光稳定性更低。观察到的颜色变化不能用降解产物的形成来解释，而是强烈依赖于原料药或制剂中的湿度水平。当将原料药制成片剂时，颜色变化显著增加（高达7倍）。在暴露前通过在低压下混合和压片观察到RF与单个片剂成分之间的相互作用。
