Verapamil-containing pulsatile delivery system based on chronotopic technology

The benefits of a chronopharmaceutical approach to the treatment of many diseases showing circadian variations in their symptomatology have lately been recognized. In this respect, bedtime administration of pulsatile release formulations designed to delay drug liberation throughout the night could prove advantageous to the therapy of chronopathologies with mainly nocturnal or early morning symptoms. This is the case of ischemic heart disease, myocardial infarction incidence being by far higher around 9 am. The Chronotopic™ system consists in a drug-containing core and an external hydrophilic swellable polymeric layer responsible for a delayed release onset. Aim of this work was to evaluate the feasibility of a low viscosity hydroxypropyl methylcellulose-based aqueous spray coating process and the in vitro release behavior relevant to the Chronotopic™ system containing verapamil as the active ingredient. Immediate as well as prolonged release tableted cores of different size were prepared and investigated in order to achieve versatile modified release performances. The obtained results seemed to suggest a potential suitability of the system for ischemic heart disease chronotherapy with improved patient compliance.