Design of experiment optimization of hydrocortisone ocular minitablets via vacuum compression molding with scalability assessment by fused deposition modeling

This study compares the in vitro performance of vacuum-compressed (VCM) and fused deposition modeling (FDM) 3D-printed ocular minitablets loaded with Hydrocortisone. Using a design of experiment (DoE) approach, 15 formulations were screened and optimized to achieve sustained release over 24 h. The optimized VCM minitablet demonstrated a surface pH of 7.38 ± 0.02, a swelling index of sixfold its initial weight (20 mg), in vitro mucoadhesion of 280 ± 6 mN, and folding endurance of 641.30 ± 11.50 cycles. Thermal analysis and FTIR confirmed the absence of chemical incompatibilities and identified drug degradation thresholds. Drug content was verified, with VCM tablets containing 100.88 ± 2.55 % and FDM tablets 85.91 ± 3.68 %. In vitro release studies revealed that both minitablet types followed Korsmeyer Peppas kinetics with Fickian diffusion, although cumulative release was higher for VCM tablets (96.74 ± 0.41 %) compared to FDM tablets (88.52 ± 4.93 %). Although the differences were not statistically significant (p = 0.10), they indicate process induced microstructural variations. Nevertheless, the VCM approach showed a comparable in vitro release profile to 3D-printed minitablets, as confirmed by the f₂ similarity test (f₂ value of 62.20). Overall, VCM produced void free minitablets at lower temperature compared to HME and FDM to achieve extrusion and printability. These elevated temperatures complicate direct scale up and raise concerns of thermal degradation for heat sensitive drugs such as hydrocortisone.