Design and development of an ethyl cellulose bulk-engineered spherule-based capsule system.

This study addresses a critical challenge in delivering a drug to prevent angina in the early morning hours, aligning with the heart's circadian rhythm. For this purpose, we formulated Isosorbide dinitrate (ISDN) - loaded spherules for delayed release (DR) followed by sustained release (SR) using ethyl cellulose by spheronization technique. DOE-led optimisation is done to develop the design of space for optimized spherules. The DR-coated spherules exhibit possible surface modifications, indicating the presence of a coating layer that can influence the release profile and provide marginally better flow characteristics (Angle of repose 31.38 ± 0.02, Carr's index 10 ± 0.35%, Hausner's Ratio 1.11 ± 0.037) compared to granules and SR spherules. In vitro drug release in pH 1.2 is 4.8% indicating negligible drug release due to DR coating, whereas, under colonic pH (7.4) conditions, initially 40% is released as a burst release and approximately 60% of ISDN is released over 24 h, which indicates that DR coating modifies the drug release profile. Following the successful modulation of release behaviour via engineering the delivery system, spherules coated with ethyl cellulose and Eudragit S-100 exhibit negligible release in pH 1.2, confirming strong resistance for release in the gastric environment. The design of space (DOS), optimized through JMP software using the Design of Experiments (DOE) approach, confirms the targeted performance. The results of the DOE to experimental validated results were within 5% deviation.