A Review of Currently Available Fenofibrate and Fenofibric Acid Formulations

Abstract

Fenofibrate is a third-generation fibric acid derivative indicated as a monotherapy to reduce elevated low-density lipoprotein cholesterol, total cholesterol, triglycerides, and apolipoprotein B; to increase high-density lipoprotein cholesterol in patients with primary hyperlipidemia or mixed dyslipidemia; and to reduce triglycerides in patients with severe hypertriglyceridemia. In this review, the key characteristics of available fenofibrate formulations are examined. A literature search was conducted, focusing on comparative studies examining bioavailability, food effects, absorption, and lipid efficacy. Fenofibrate is highly lipophilic, virtually insoluble in water, and poorly absorbed. Coadministration with meals was necessary to maximize bioavailability of early formulations. Micronized and nanoparticle formulations of fenofibrate with reduced particle sizes were developed, resulting in greater solubility, improved bioavailability, and in some cases, the ability to be given irrespective of food. A recently introduced hydrophilic choline salt of fenofibric acid also can be taken without regard to meals, is absorbed throughout the gastrointestinal tract, has the highest bioavailability among marketed formulations, and is approved for coadministration with a statin. Differences in bioavailability of fenofibrate formulations have resulted in low-dose (40 -67) mg and standard-dose (120 -200 mg) formulations. Different formulations are not equivalent on a milligram-to-milligram basis. In order to prevent medication errors, resulting in underdosing or overdosing with attendant consequences, it is important for healthcare providers to recognize that the formulations of fenofibrate and fenofibric acid that are currently available vary substantially in relation to food effect, equivalency on a milligram-to-milligram basis, and indication to be coadministered with a statin.

The Lidose Hard Capsule Formulation of Fenofibrate is Suprabioavailable Compared to the Nanoparticle Tablet Formulation Under High-fat Fed Conditions

“…Fenofibrate was first introduced in 1975 but the oral bioavailability of this standard formulation was very low especially when taken without a high-fat meal (6,9). Micronized fenofibrate formulations were subsequently developed to increase the water solubility and hence the oral bioavailability of fenofibrate (2).…”

“…The Lidose drug delivery technology, i.e. a hard capsule with a semi-solid content into which fenofibrate is homogeneously dispersed within a lipid excipient mixture, was also used in an attempt to improve the oral fenofibrate bioavailability (9). Despite improvement in oral bioavailability of the micronized fenofibrate tablets and Lidose fenofibrate hard capsules, these formulations still require the presence of food, particularly a highfat meal, to maximize the extent of fenofibrate absorption (2,9).…”

“…This product was considered to be bioequivalent to the 200 mg micronized fenofibrate reference product on the basis of a crossover relative bioavailability study (8). A major drawback of all these fenofibrate formulations is that adequate oral absorption requires their administration with a high-fat meal (9)(10)(11). More recently, a new nanoparticle tablet formulation of fenofibrate has become available in 48 mg and 145 mg dose strengths (12,13).…”

“…Consequently, marketed oral fenofibrate formulations may not only differ substantially in available dose strengths, but also in the requirement to be taken with a meal (9). The present bioequivalence study was undertaken to investigate the bioavailability of a 145 mg fenofibrate nanoparticle tablet relative to the 200 mg fenofibrate Lidose hard capsule when administered to healthy volunteers under high-fat conditions.…”

Nanotherapeutics in the EU: an overview on current state and future directions

“…42 In addition, tablets containing fenofibrate nanocrystals significantly reduce its required dose (145 mg) compared with tablets (160 mg) and capsules (200 mg) containing micronized and non-micronized fenofibrate, respectively. 44 virosomes Virosomes are a drug or vaccine delivery system composed of viral membranes that are reconstituted with viral lipids and proteins, allowing the fusion with target cells (Figure 2). 45 Virosome production generally includes detergent solubilization of the influenza virus and subsequent reconstitution with two influenza envelope glycoproteins, hemagglutinin and neuraminidase.…”