Cardiovascular diseases (CVDs) are disorders associated with heart and blood vessels and are considered as the leading cause of morbidity and mortality worldwide (Bhatnagar 2015). The main risk factors associated with CVDs are smoking, hypertension and dyslipidaemia to mention few. Amongst them, dyslipidaemia is considered as the dominant risk factor (Yusuf 2001, Nelson 2013). Despite the fact that management of dyslipidaemia can be attained using different anti-hyperlipidemics such as statins, niacin, fibrates and bile acids, statins are considered as first line therapy (Whalen 2014). Simvastatin (SIM) is the most prescribed statin among others, nevertheless, due to its poor solubility and its susceptibility to metabolism by CYP 3A4, SIM is poorly bioavailable after oral administration (only 5% reaches the systemic circulation). Along with statins, long-term therapy with low-dose aspirin (ASP), is highly effective for the secondary prevention of cardiovascular (CV) events. The main concern associated with multiple therapy, however, is the poor adherence to medications. An efficient approach to overcome the poor adherence is by formulating multiple APIs into single dosage forms in fixed dose combinations (FDC). In this study, hot melt co-extrusion (HMCE) was used as a platform to manufacture a bi-layer concentric co-extrudate. These co-extrudates contain a FDC of ASP and (SIM) dispersed in the coat/core layers, respectively. The polymeric matrix of the coat is designed to release ASP immediately in the stomach, while the core layer is intended to release SIM in the proximal regions of the small intestine.
Gilvary, G. C., Dec 2020
Student thesis: Doctoral Thesis › Doctor of Philosophy