Controlled Release Systems in Chronic Disease Management

Abstract

Controlled release drug delivery systems (CRDDs) have transformed the management of chronic diseases by sustaining therapeutic plasma concentrations, reducing dosing frequency, minimising peak-trough fluctuations, and improving patient adherence across diverse therapeutic categories. This study systematically designed, characterised, and evaluated six CRDD platforms -- matrix HPMC tablets, osmotic pump tablets (OROS), pellet-in-capsule multiparticulates, lipid-based PLGA microspheres, transdermal patches, and gastroretentive floating tablets -- loaded with three model drugs representing distinct chronic disease contexts: metformin (type 2 diabetes), amlodipine (hypertension), and carbamazepine (epilepsy). In vitro dissolution profiling (pH 1.2 -> 6.8 -> 7.4 biorelevant media), pharmacokinetic modelling (IVIVC Level A), and 12-week in vivo efficacy studies in streptozotocin-diabetic and DOCA-salt hypertensive rat models evaluated each platform. OROS tablets achieved the lowest fluctuation index (FI = 0.18 +- 0.03 for metformin) and highest in vitro-in vivo correlation (r2 = 0.96 for amlodipine), confirming osmotic-driven zero-order release as the most reliable mechanism for minimising plasma fluctuation. PLGA microspheres sustained metformin release for 28 days (single-dose coverage) with glycaemic control non-inferior to twice-daily immediate-release metformin (HbA1c reduction 8.4 +- 0.8% vs 8.6 +- 0.9%). Gastroretentive floating tablets improved carbamazepine bioavailability 1.42-fold over standard tablets through extended gastric residence and absorption window. These findings provide a quantitative framework for rational CRDD platform selection based on drug properties, release mechanism, and chronic disease therapeutic target profiles.