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

Abstract

-Purpose:The therapeutic equivalence of multiple registered fenofibrate formulations, several of which are suprabioavailable and therefore marketed at lower dosage strengths than their reference products, is based on the results of bioequivalence studies. Most of these formulations show a higher bioavailability when taken with a high-fat meal. The relative bioavailability of two of these formulations, the 200 mg Lidose hard capsules and the 145 mg nanoparticle tablets, was assessed when taken with a high-fat meal. Methods: In this single dose, 2-way, randomized, crossover study, 24 healthy subjects received a 200 mg fenofibrate Lidose hard capsule (Test) and a 145 mg nanoparticle tablet (Reference) under high-fat fed conditions. Plasma concentrations of fenofibric acid were measured up to 72 hours by using a validated LC-MS/MS method. Results: The geometric mean ratios (Test/Reference) and the 90% confidence intervals for AUC0-t and Cmax were 1.37 (131.58 -142.88) and 1.38 (124.60 -152.93), respectively. The median (range) Tmax values of fenofibric acid were 4.5 h (3.0 -8.0 h) and 3.25 h (1.0 -6.5 h) after administration of the Lidose hard capsule and the nanoparticle tablet, respectively. Conclusion: Under high-fat fed conditions the extent of fenofibrate absorption was 37% higher for the 200 mg Lidose hard capsule compared to the 145 mg nanoparticle tablet, which is exactly as expected based on a mg-to-mg weight basis. The results of the present study underline the importance of assessing bioequivalence of fenofibrate formulations under identical fed conditions, and preferentially after a high-fat meal as this condition represents the worst-case scenario. Furthermore, the results of this study demonstrate that the 145 mg nanoparticle tablet is not bioequivalent to the 200 mg Lidose hard capsule when administered under high-fat meal conditions.

The Influence of Fed State Lipolysis Inhibition on the Intraluminal Behaviour and Absorption of Fenofibrate from a Lipid-Based Formulation

“…On the other hand, fenofibrate is on the market as the LBF Fenogal. Fenogal contains homogeneously dispersed fenofibrate (200 mg) within a lipid excipient mixture (Gelucire 44/14) and can be classified as a class IIIb formulation according to the Lipid Formulation Classification System (LFCS) [6]. Gelucire 44/14 is a semi-solid self-emulsifying lipid excipient, composed of C8-C18 MAGs, DAGs and TAGs (solubilisation), C8-C18 mono-and diesters of PEG-32 (surfactants) and free PEG-32 (co-solvent), which forms a finely dispersed microemulsion when in contact with the aqueous environment of the GI tract [7].…”

“…Gelucire 44/14 is a semi-solid self-emulsifying lipid excipient, composed of C8-C18 MAGs, DAGs and TAGs (solubilisation), C8-C18 mono-and diesters of PEG-32 (surfactants) and free PEG-32 (co-solvent), which forms a finely dispersed microemulsion when in contact with the aqueous environment of the GI tract [7]. Although elimination of a food effect can be observed in vivo for some compounds formulated as LBFs [8][9][10], Fenogal still needs to be taken with a meal to enhance the oral bioavailability of fenofibrate [6]. In theory, both acylglycerols and PEG esters are substrates for digestive enzymes.…”

Modern possibilities of using systemic retinoids in dermatological practice (review of international literature)

“…Это позволяет снизить суточные и курсовые дозы изотретиноина LIDOSE на 20%: рекомендованный диапазон суточных доз CИ, произведенного по технологии LIDOSE, составляет 0,4-0,8 мг/кг, курсовых доз -100-120 мг/кг. Уменьшение разовой и курсовой дозировки изотретиноина на 20% с полным сохранением терапевтической эффективности обусловливает уменьшение числа побочных эффектов [48,49]. Изотретиноин плохо растворим в воде, поэтому всасывание препарата происходит лучше при его приеме с пищей.…”

Development and validation of a rapid UHPLC-MS/MS method for the determination of fenofibric acid in human plasma: Application to a pharmacokinetic study of fenofibrate tablet in Chinese subjects

“…Recent bench studies have demonstrated an array of cardiovascular and renal pleiotropic beneficial activities of fenofibrate, besides its foremost lipid-lowering action [1,2]. There are many available formulations of fenofibrate on the market, such as micronized capsules and tablets, nanocrystal tablets, and fenofibric acid (FA) capsules (delayed-release) [3][4][5]. The pharmacokinetic studies of these preparations have been conducted in many countries, however, the pharmacokinetic studies of fenofibrate tablets (Lipanthyl ® supra, 160 mg) in Chinese subjects have not been reported.…”