Whilst monotherapy is traditionally the preferred treatment starting point for chronic conditions such as hypertension and diabetes, other diseases require the use of multiple drugs (polytherapy) from the onset of treatment (e.g., human immunodeficiency virus acquired immunodeficiency syndrome, tuberculosis, and malaria). Successful treatment of these chronic conditions is sometimes hampered by patient non-adherence to polytherapy. The options available for polytherapy are either the sequential addition of individual drug products to deliver an effective multi-drug regimen or the use of a single fixed-dose combination (FDC) therapy product. This article intends to critically review the use of FDC drug therapy and provide an insight into FDC products which are already commercially available. Shortcomings of FDC formulations are discussed from multiple perspectives and research gaps are identified. Moreover, an overview of fundamental formulation considerations is provided to aid formulation scientists in the design and development of new FDC products.

Highly lipophilic antimalarial drugs, artemether and lumefantrine, whilst an effective fixed-dose combination treatment to lower the malarial disease burden, are therapeutically hindered by low aqueous solubility and varied bioavailability. This work investigates the plausibility of directly compressed lipid matrix tablets, their role as lipid-based formulations and their future standing as drug delivery systems. Lipid matrix tablets were manufactured from solid lipid dispersions in various lipid:drug ratios employing hot fusion—the melt mixing of highly lipophilic drugs with polymer(s). Sequential biorelevant dissolution media, multiple mathematical models and ex vivo analysis utilizing porcine tissue samples were employed to assess drug release kinetics and more accurately predict in vitro performance. Directly compressed stearic acid tablets in a 0.5:1 lipid:drug ratio were deemed optimal within investigated parameters. Biorelevant media was of immense value for artemether release analysis, with formulation SA0.5C1 (Stearic Acid:double fixed dose in a 0.5:1 ratio (i.e., Stearic acid 70 mg + Lumefantrine 120 mg + Artemether 20 mg); CombiLac^® as filler (q.s.); and 1% w/w magnesium stearate) yielding a higher percentage of artemether release (97.21%) than the commercially available product, Coartem^® (86.12%). However, dissolution media lacked the specificity to detect lumefantrine. Nonetheless, stearic acid lipid:drug ratios governed drug release mechanisms. This work demonstrates the successful utilization of lipids as pharmaceutical excipients, particularly in the formulation of lipid matrix tablets to augment the dissolution of highly lipophilic drugs, and could thus potentially improve current malarial treatment regimens.