Development of the formulation and manufacturing process of lozenges with Ajania fruticulosa (Ledeb.) Poljak dry extract using the Quality by Design concept

Introduction. This article presents the development of a technology for obtaining lozenges containing Ajania fruticulosa dry extract using the direct compression method. The Quality by Design (QbD) concept reflects a modern approach to pharmaceutical development based on the identification and control of Critical Quality Attributes (CQA) and Critical Process Parameters (CPP) that determine their variability. The application of Design of Experiments (DoE) allows for the quantitative assessment of the influence of technological variables and their interactions, optimization of production conditions, reduction of experimental series volume, and ensuring the control of the technological process. Aim. To develop the composition and technology of lozenges with Ajania fruticulosa dry extract using the direct compression method and applying the principles of the QbD concept. Materials and methods. A standardized Ajania fruticulosa dry extract, obtained by maceration with ultrasonic intensification in accordance with the EAEU Pharmacopoeia, was used as the Active Pharmaceutical Ingredient (API). The lozenges were obtained by the direct compression method with varying concentrations of talc (0.1–3.0 %), copovidone (2.0–5.0 %), and compression pressure (15–30 kN). Disintegration time and friability were chosen as the CQAs. Experimental design and statistical analysis were performed using Minitab Statistical Software 22.3.0 (LLC "Minitab", USA) with the DoE module. Disintegration time and friability were determined in accordance with the requirements of the EAEU Pharmacopoeia using ZT 320 and TAR 220 apparatuses (ERWEKA GmbH, Germany). Results and discussion. The optimal API concentration was 1.5 %. According to the DoE results, the copovidone content and compression pressure had a statistically significant effect on the disintegration time, while the contribution of talc was insignificant. The optimal parameters were: copovidone – 5 %, talc – 2 %, compression force – 22 kN. Under these conditions, the disintegration time was 12.9 min, friability was 0.50 %, and the overall desirability index D = 0.8168. Conclusion. The implementation of the QbD concept in combination with DoE provided a scientifically grounded approach to the development of lozenges with Ajania fruticulosa dry extract. The developed lozenges meet the requirements of the EAEU Pharmacopoeia and are recommended for scale-up and industrial production.