Effect of magnesium carbonate on the solubility, dissolution and oral bioavailability of fenofibric acid powder as an alkalising solubilizer

Abstract

To investigate the possibility of developing a novel oral pharmaceutical product using fenofibric acid instead of choline fenofibrate, the powder properties, solubility, dissolution and pharmacokinetics in rats of fenofibrate, choline fenofibrate and fenofibric acid were compared. Furthermore, the effect of magnesium carbonate, an alkalising agent on the solubility, dissolution and oral bioavailability of fenofibric acid was assessed, a mixture of fenofibric acid and magnesium carbonate being prepared by simple blending at a weight ratio of 2/1. The three fenofibrate derivatives showed different particle sizes and melting points with similar crystalline shape. Fenofibric acid had a significantly higher aqueous solubility and dissolution than fenofibrate, but significantly lower solubility and dissolution than choline fenofibrate. However, the fenofibric acid/magnesium carbonate mixture greatly improved the solubility and dissolution of fenofibric acid with an enhancement to levels similar with those for choline fenofibrate. Fenofibric acid gave lower plasma concentrations, AUC and Cmax values compared to choline fenofibrate in rats. However, the mixture resulted in plasma concentrations, AUC and Cmax values levels not significantly different from those for choline fenofibrate. Specifically, magnesium carbonate increased the aqueous solubility, dissolution and bioavailability of fenofibric acid by about 7.5-, 4- and 1.6-fold, respectively. Thus, the mixture of fenofibric acid and magnesium carbonate at the weight ratio of 2/1 might be a candidate for an oral pharmaceutical product with improved oral bioavailability.

Efficacy and Safety of Fenofibrate-Statin Combination Therapy in Patients With Inadequately Controlled Triglyceride Levels Despite Previous Statin Monotherapy: A Multicenter, Randomized, Double-blind, Phase IV Study

“…12 Therefore, choline fenofibrate can be taken regardless of food, whereas traditional fenofibrate needs to be taken immediately after meals. 13 After 8 weeks of combination therapy, there was a 45.57% reduction in TG levels, and 65.57% of the patients achieved the target TG level of 150 mg/dL. The pharmacologic potency of choline fenofibrate in this study is not inferior to that reported in previous studies.…”

Enhanced Chemical Stability of D‐Cycloserine via Tablet Form Containing Magnesium Oxide as an Alkali Stabilizer

“…First, to investigate the enhancement of stability of D‐cycloserine via alkalizing agents, the mixtures of D‐cycloserine and each alkalizing agent were stored at the accelerated stress condition of 60 °C/75% RH for 2 days, and the remaining concentrations of D‐cycloserine were determined . Meglumine, precipitated calcium carbonate, magnesium oxide, sodium bicarbonate, calcium silicate, magnesium aluminosilicate, and sodium citrate dehydrate were employed as the alkalizing agents . The remaining concentrations in the D‐cycloserine alone was nearly 0% (Figure ), suggesting that D‐cycloserine were very unstable in this accelerated stress condition.…”

Dissolution enhancement and physicochemical characterization of fenofibric acid in surface solid dispersion with croscarmellose sodium

“…Figure 2 illustrates the X-ray diffractions of the samples. The diffractogram indicates that the pure FA is crystalline as demonstrated by specific peaks at the diffraction angles (2θ) of 18°, 19°, 21°, and 23° [9] with crystallinity value 86.69%. According to the XRD pattern, the recrystallized FA had more diverse peak intensities than the pure FA, and only one peak appeared at (2θ) 23° with crystallinity value 79.90%.…”