Current Status of Development of Oral Formulations Combining Omega-3 Fatty Acids and Statin Ingredients and Prospects for New Formulations

Abstract

Background

Omega-3 fatty acids (O3FA) and statins effectively reducing the levels of triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C), respectively, and are actively used in clinical practice worldwide for the treatment of hyperlipidemia. Combinations of O3FA and statins have been found effective in managing complex dyslipidemia cases and achieving synergistic therapeutic effects while improving patient compliance.

Purpose

This study was conducted to examine the current status of the development of combinations of O3FA and statins, which have recently been garnering attention, and to consider future approaches to developing additional formulations.

Methods

By reviewing published literature and market reports, we summarize the development status of O3FA and statin combinations. We also identified a scope for improvement in such formulations and propose new formulation development approaches.

Results

Co-administration of direct physical combinations of O3FA and statins is generally considered safe and free of drug interactions, but inherent challenges to drug stability exist. In particular, O3FA oxidation is highly possible, necessitating a spatially separated combination technology without direct contact with statins. An attempt to encapsulate O3FA within soft capsules and statin drugs as powders, granules, or tablets in a hollow capsule was proposed as a new approach that can solve both the stability issues due to potential interactions between ingredients and the content change issues due to ingredient loss during mechanical transport. In addition, a novel combination formulation with fibrate or ezetimibe was proposed to improve TG, cholesterol, and LDL-C levels while maximizing compliance in patients taking multiple medications.

Conclusion

Attempts to formulate combinations of anti-hyperlipidemic drugs are becoming popular in the management of complex dyslipidemia cases. In this context, this study presents important pharmaceutical perspectives on combining O3FA and statins. The findings presented herein provide useful insights into developing additional improved oral formulations in the future.