Development of approaches to improve the photostability of model tablets N-benzyl-N-methyl-1-phenylpyrrolo[1,2-a]pyrazine- 3-carboxamide

Background. Photostability is one of the key characteristics of an active pharmaceutical ingredient (API) in the development of a medicinal product. If photodestruction processes are detected, it is necessary to find ways to prevent them in order to ensure the stability of API and drugs based on it.
Objective. To develop of technological approaches to increase the photostability of N-benzyl-N-methyl-1-phenylpyrrolo[1,2-a]pyrazine-3-carboxamide (GML-1) APIs in tablets for oral use.
Materials and methods. The study subjects were GML-1 cores and film-coated tablets (Opadry®QX — 321A220002 Yellow, Opadry®QX — 03K510010 Green, Opadry®II — 57U110000 Green), two types of primary packaging (amber glass bottles and polymer containers), and secondary packaging (cardboard cartons). A TP-R type coater was used for film coating. Photostability was assessed using an ATLAS SUNTEST CPS+ test chamber equipped with an ATLAS Sun Cool cooling system. Related impurity content was determined by high-performance liquid chromatography.
Results. Optimal process parameters for applying three film coatings with light-absorbing and light-reflecting pigments to GML-1 tablet cores were determined. Photostability tests revealed that GML-1 degradation was observed in both the cores and unpackaged tablets with all three film coatings. However, differences in the levels of related impurities identified the superior film coating — Opadry®QX 321A220002 Yellow, which contains the highest titanium dioxide content and added yellow iron oxide. In tablets coated with this coating and packaged in polymer jars or dark glass jars, a slight increase in the content of related impurities was also observed compared to the control sample; however, when using secondary packaging in the form of cardboard packs, the formation of new impurities was almost completely prevented.
Conclusions. To protect the GML-1 model tablets from light, the optimal film coating, Opadry®QX — 321A220002 Yellow (at a rate of 5 % of the core weight), was identified and a coating application technology developed. Light-protective packaging was selected: polymer jars or dark glass bottles placed in a cardboard box.

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