Optimization of gemifloxacin immediate-release tablets using quality by design.

The objective of this study is to determine the design space (DS) for a dissolution-enhanced gemifloxacin immediate-release (IR) tablet incorporating hydroxypropyl-β-cyclodextrin (HPCD) for improved solubility, utilizing a quality by design (QbD) approach. Based on the preliminary studies, hardness, friability, disintegration time, assay, content uniformity, and dissolution rate were identified as the critical quality attributes (CQAs) for optimization. Through the initial risk assessment, crospovidone, main compression force, and the amount of granulating fluid were identified as factors influencing the CQAs, and a 23 + 3 full factorial design of experiments (DoE) was conducted for optimization. According to the analysis of variance (ANOVA), both main compression force (p = 0.004) and the amount of granulating fluid (p = 0.001) significantly affected hardness. While the amount of granulating fluid was established as a primary factor influencing disintegration time (p = 0.001) and dissolution rate (p = 0.006). The other factors did not show a statistically significant impact on the remaining CQAs. The optimized ranges obtained from this study were as follows: crospovidone, 5.72-7.99%; main compression force, 1707.5-2372.3 kgf; and amount of granulating fluid, 5.36-6.12 mL. A 23 + 3 full-factorial design of experiments (DoE) was applied to determine the relationship between independent and dependent variables, and a high-quality IR tablet meeting all predefined CQA criteria [hardness (18.0-22.0 kp), friability (≤0.5%), disintegration time (16.0-20.0 min), assay (95.0-105.0%), content uniformity (AV ≤ 5), and dissolution similarity (f2 ≥ 50)] was developed through the systematic optimization of formulation and manufacturing processes.