PHARMACEUTICAL ASPECTS OF THE DEVELOPMENT OF SINGLE-STRANDED YEAST RNA–ASCORBIC ACID COMPLEXES. PART 1. PHYSICOCHEMICAL CHARACTERISTICS AND CRITICAL QUALITY ATTRIBUTES

Aim. To systematize current data on single-stranded yeast RNA–ascorbic acid complexes as objects of pharmaceutical chemistry, to describe their physicochemical features and to define critical quality attributes (CQAs) that determine requirements for the development and quality control of dosage forms of this class. Material and methods. An analytical review of publications on the structure and polydispersity of yeast RNA, the chemistry and degradation of ascorbic acid, and modern regulatory approaches to the quality of biotechnological and RNA-based products (including ICH Q6B, Q5C) was performed. On this basis, the composition of the yeast ssRNA–ascorbate complex, the nature of interactions between its components and the impact of environmental factors (pH, temperature, water, oxygen, metal ions) on its stability were analysed conceptually. Results. The single-stranded yeast RNA–ascorbic acid complex was shown to be a dynamic system in which the physicochemical behavior of the RNA fraction and ascorbic acid is interdependent and governed by the intrinsic properties of the components and matrix parameters. For the RNA component, a set of CQAs was proposed, including substance origin and identity, chain-length distribution profile, integrity of the polymer fraction, product- and process-related impurities, residual DNA and proteins. For ascorbic acid, CQAs related to content, uniformity of dosage, profiles of major degradation products and medium parameters determining its redox behavior were identified. At the level of the finished dosage form, a structured CQA panel combining physicochemical, microbiological and stability-indicating parameters was outlined. Conclusion. Single-stranded yeast RNA–ascorbic acid complexes should be regarded as objects of pharmaceutical chemistry and dosage form technology with clearly defined critical quality attributes. The CQA framework developed in this first part provides the basis for selecting analytical methods and designing stability studies, which will be discussed in detail in the second part of the review series.