Fixed Dose Combination Formulations: Multi-Layered Platforms Designed for the Management of Cardiovascular Disease

Hyperlipidaemia is considered as one of the main risk factors associated with cardiovascular diseases (CVDs). Among different lipid-lowering agents used to manage hyperlipidaemia, statins are highly prescribed for management of hyperlipidaemia with simvastatin being one of the most common. Simvastatin is susceptible to extensive metabolism by CYP450 3A4 and 3A5 which are expressed both in the liver and the gastrointestinal tract. Nevertheless, the localization of these enzymes is site dependent with lower concentration at the distal/proximal regions of the small intestine/colon. In addition to statins, medications such as antihypertensive and anti-coagulants are introduced as adjuvants, for the treatment of cardiovascular disease. The aim of this study was to design a bi-layer delivery system capable of delivering bi-phasic release of Simvastatin and Aspirin, within a fixed dose combination. A delayed release platform based on a combination of anionic polymers prepared using hot melt extrusion was developed to delay the release of simvastatin. An optimized formulation was tested for dissolution performance clearly demonstrated an ability to delay the release of Simvastatin. In addition, an immediate release layer based on Kollidon VA64 was successfully developed to deliver Aspirin. Both formulations were then manufactured as a bi-layer drug delivery system (tablets and co-extrudates) and the release performance examined. Based on the obtained results, these formulations may be used as a platform for the delivery wide range of medications in a bi-phasic manner.