Chronotherapeutic disorders such as hypertension, cardiovascular disease and asthma commonly involve the use of controlled zero-order release formulations. Ideally, the required drug should be released at predetermined rates with two or more pulses released from the dosage form. This ultimately exposes the patient to drug only when required, reducing the number of dosages, reducing side-effects and increasing patient compliance. The aim of this research was to evaluate two Multi-Layered Multi-Disk Tablet (MLMDT) systems incorporating drug-loaded disks enveloped by three polymeric layers. The model drugs used for each system were theophylline and diltiazem hydrochloride. The proposed chronotherapeutic system was designed to provide a lag phase and then two pulses of drug release separated by a ‘switch-off’ phase. In vitro drug release analysis revealed that the MLMDT generated a lag phase or a ‘switch-off’ phase followed by two pulses of drug release over the evaluated 24 h period. In vivo testing was undertaken using a Large White Pig Model, where concentration analysis from the evaluated conventional products revealed increasing plasma concentrations up to 2 h followed by a steady decline in concentration while the developed MLMDT displayed two pulse prolonged drug release profile separated by a switch-off phase.