FORMULATION AND EVALUATION OF A CHRONOMODULATED PULSATILE TABLET DRUG DELIVERY SYSTEM OF DESIPRAMINE HYDROCHLORIDE

AbstractBackground: Depressive symptoms frequently show a circadian rhythm, often worsening in theearly morning, yet conventional immediate-release antidepressants deliver drug without regard tothis biological timing. A chronomodulated pulsatile system that releases drug after aprogrammed lag—timed to bedtime administration—could better synchronise therapy withsymptom rhythm.Objective: To formulate and evaluate compression-coated pulsatile tablets of desipraminehydrochloride designed to provide a predetermined lag time followed by rapid drug release forcircadian management of depression.Methods: Immediate-release desipramine cores (25 mg drug; 100 mg) were prepared by directcompression and press-coated with blends of HPMC K100M, ethyl cellulose and sodiumalginate to a total tablet weight of 300 mg, generating nine formulations (F1–F9) that variedHPMC K100M (60–80 mg) and ethyl cellulose (40–60 mg) at a fixed sodium alginate level (20mg). Preformulation included organoleptic examination, UV λmax determination, calibration andFTIR drug–excipient compatibility. Coating blends were assessed for angle of repose, bulk andtapped density, Carr’s index and Hausner’s ratio; tablets were evaluated for weight variation,thickness, hardness, friability, drug content, swelling index, lag time, rupture time and two-stage(0.1 N HCl then pH 6.8) in vitro release.Results: Desipramine showed λmax 251 nm with linear calibration (y = 0.0476x + 0.0487; R² =0.9947). FTIR confirmed retention of characteristic drug peaks in the formulation mixture,indicating compatibility. All coating blends showed good flow (angle of repose 27.18–31.63°;Carr’s index 15.38–19.08%; Hausner’s ratio 1.18–1.24), and all tablets met pharmacopeial limits(friability 0.47–0.76%; drug content 97.68–100.64%). Lag time increased with polymer contentfrom 2.4 to 7.5 h, with rupture times of 2.7–7.9 h and swelling index 77.4–155.3%. Release waspulsatile: lower-polymer batches released early, while F7 restricted release to <2% through 5 hand <19% at 6 h, then released rapidly (67.82% at 7 h; 99.68% at 11 h), giving a lag ofapproximately 6–6.5 h.Conclusion: Compression coating with HPMC K100M, ethyl cellulose and sodium alginateproduced robust chronomodulated pulsatile tablets of desipramine, with lag time tunable through polymer composition. Formulation F7 best matched the chronotherapeutic target for earlymorning symptom control and was selected as the optimized batch.