Hot-Melt Co-extrusion Technology as a Manufacturing Platform for Anti-hypertensive Fixed-Dose Combinations

Hypertension (HYP) accounts for 9.4 million deaths worldwide annually and requires the long-term use of medicines as part of complex drug regimens. While marketed anti-hypertensive medications containing active pharmaceutical ingredients (APIs) have been clinically proven to be effective in the treatment of HYP, their full benefits are often not realised due to poor medication adherence . There are several factors which exist for poor medication adherence including those related to the patient i.e. increased age or a lack of understanding of their disease state. It is generally accepted that adherence becomes poorer as the number of medicines prescribed is increased. This is a particular problem in the treatment of HYP, as it generally requires multiple drugs for a positive clinical outcome. Therefore, the industry has attempted to overcome this burden by combining various APIs into a single pill, which are commonly referred to as fixed-dose combinations (FDCs). Recently, hot-melt (co)-extrusion (HMCE) has received considerable attention from the pharmaceutical industry for the production of FDCs, due to its ability in designing multi-layered FDCs in a single processing step. Furthermore, HMCE products are capable of independently modulating the release of the incorporated APIs. This investigation utilises HMCE to manufacture a multi-layered FDC containing hydrochlorothiazide (HCTZ) and losartan potassium (LK). These APIs are recommended to be used in combination once-a-day for the treatment of HYP, as they have been shown to be well tolerated and more efficacious in lowering blood pressure (BP) than monotherapy.