Optimization of ticagrelor tablet for gastro-retentive drug delivery using full factorial design

Purpose: To identify the optimized region of formulation using quality by design for developing ticagrelor gastro-retentive (GR) tablets. Methods: A 23 + 3 full factorial design of experiments study was used to identify three factors (polyethylene oxide (PEO), compression, and volume of granulating fluid) involved in the wet granulation and compression process of ticagrelor GR tablets. Hardness, friability, content, dosage unit uniformity, and pH 1.2 dissolution rate (at 4, 8, and 12 h) were evaluated as critical quality attributes via analysis of variance using Design Expert software. Results: All seven models were significantly influenced based on analysis of variance results (p < 0.05). Hardness and friability were significantly affected by compression (p < 0.0001). Content uniformity was significantly affected by the interaction between compression and granulating water volume for wet granulation (p < 0.05), and dosage unit uniformity was significantly affected by the volume of granulating fluid for wet granulation (p < 0.05). However, all results were within acceptable ranges. Polyethylene oxide (PEO) (4 h, p < 0.05; 8 h, p < 0.05; 12 h, p < 0.05) and compression (4 h, p < 0.05; 8 h, p < 0.05; 12 h, p < 0.05) had negative effect on pH 1.2 dissolution rate. Conclusion: Design of experiment (DoE) approach has been used to optimize region of PEO, compression, and volume of granulating fluid for formulation development. This outcome is expected to be a basis for further research to develop TCG GR tablets on a large production scale.