Randomised Crossover Studies of the Bioequivalence of Two Fenofibrate Formulations after Administration of a Single Oral Dose in Healthy Volunteers

Abstract

Bioequivalence of a newly developed semi-solid formulation (Lidose) of fenofibrate (CAS 49562-28-9), and a reference, micronized formulation of fenofibrate was investigated in two randomised, open-label clinical studies with a crossover design. Both studies involved two distinct groups of 24 healthy volunteers. Doses of 67 mg and 200 mg, respectively, were used in study 1 and study 2. On day 1, a single oral dose was administered to all subjects, using one of the two formulations to be compared. Single oral dosing with the other formulation occurred after a washout period of at least 8 days. Blood samples were taken after each dosing for measurement of plasma fenofibric acid concentrations by high-performance liquid chromatography (HPLC) combined with fluorescence detection, and plasma pharmacokinetic parameters were determined. No statistically significant differences were noted for Cmax, Tmax, AUC0-t and AUC0-variation of between subjects treated with the new formulation and those receiving the reference formulation. Side effects were mild and not significantly different between the two fenofibrate preparations. These two studies based on validated methods demonstrate that the new and the reference fenofibrate formulations are bioequivalent when administered at the two doses studied.

In situ formation of nanocrystals from a self-microemulsifying drug delivery system to enhance oral bioavailability of fenofibrate

“…The resulting formulation has increased drug solubility and dissolution rates as well as improved oral bioavailability equivalent to micronized FFB formulations. 34 A SMEDDS composed of Labrafac TM (Gattefossé, Lyon, France) CM10 (31.5%), Tween ® 80 (ICI Americas Inc) (47.3%), and polyethylene glycol 400 (12.7%) was formulated for FFB and produced significant reductions in serum lipid levels in Phases I and II of the Triton test compared with plain FFB. 35 Based on the previous study, 36 the authors of the present study were intrigued that microemulsifying SMEDDSs in an aqueous medium or gastrointestinal tract fluid could decrease the drug loading, causing the solubilized FFB in the SMEDDS preconcentrate to precipitate.…”

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

“…When the bioavailability of a 67 mg and 200 mg Lidose hard capsules was compared to that of the 67 mg and 200 mg micronized fenofibrate capsules, the Lidose 67 mg and 200 mg formulations were shown to be bioequivalent to the 67 mg and 200 mg micronized fenofibrate capsules, respectively, under high-fat fed conditions (8). In the bioequivalence study described in this publication, the bioavailability of a 145 mg fenofibrate nanoparticle tablet was compared to that of a 200 mg fenofibrate Lidose hard capsule under high-fat fed conditions.…”

“…In the bioequivalence study described in this publication, the bioavailability of a 145 mg fenofibrate nanoparticle tablet was compared to that of a 200 mg fenofibrate Lidose hard capsule under high-fat fed conditions. Based on the results of the above described bioequivalence studies (8,18) During the last 20 years several reformulations of the marketed branded fenofibrate preparations have been developed as well as generics of out of patent fenofibrate preparations. Registration of these reformulated and generic fenofibrate preparations was based mainly on bioequivalence studies to show therapeutic equivalence between the reformulated or generic preparation and a marketed reference formulation.…”

“…SMB-Galephar (Brussels, Belgium) developed a 200 mg hard capsule formulation with a semi-solid content (Lidose, patent EP 0801562B1) into which fenofibrate is homogeneously dispersed within a lipid excipient mixture (7). 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).…”

The apparent solubilizing capacity of simulated intestinal fluids for poorly water-soluble drugs

“…High bSR can also be a rationale for the development of a formulation that potentially reduces the effects of food intake on drug solubility and absorption. As an example, fenofibrate was successfully formulated as lipid-based drug delivery system [33,34] and as a micro particle system, for which a clear reduction of food effects was clinically reported. [35,36] …”