Comparative Bioavailability Study of Solid Self-Nanoemulsifying Drug Delivery System of Fenofibric Acid in Healthy Male Subjects.

OBJECTIVE: This study aimed to evaluate the effect of solid self-nanoemulsifying drug delivery system (S-SNEDDS) formation on the bioavailability of fenofibric acid. SUBJECT AND METHODS: Three formulations of fenofibric acid, namely, S-SNEDDS containing medium-chain triglyceride (FS1), S-SNEDDS containing long-chain triglyceride (FS2), and FSt as tablet of innovator product, were used in this study. Bioavailability study was conducted in 12 Indonesian healthy male subjects after a single-dose administration of each formulation with three-way crossover design. Blood samples were collected from 0 to 72 h after drug administration and then analyzed using the high-performance liquid chromatography method. Data were statistically analyzed using the ANOVA and the Wilcoxon signed-rank test using a p value of 0.05. Dissolution test was carried out with USP dissolution apparatus using three medium (pH 1.2, 4.5 and 6.8). RESULTS: The rates of absorption of fenofibric acid from S-SNEDDS FS1 and FS2 were significantly increased about 1.78 and 2.40 times, respectively, relative to FSt. Tmax values of FS1 and FS2 were shorter than FSt, namely, 0.96 ± 0.438 h (FS1), 0.71 ± 0.445 h (FS2), and 1.71 ± 0.840 h (FSt), respectively. Meanwhile, the Cmax and AUC values of FS1, FS2, and FSt were found to be not significantly different with a p value of >0.05. S-SNEDDS formation increased the dissolution rate in acid medium. CONCLUSIONS: S-SNEDDS increased the dissolution rate in acid medium and absorption rate of fenofibric acid but did not increase the extent of fenofibric acid absorption.

Comparative In Vitro and In Vivo Evaluation of Fenofibric Acid as an Antihyperlipidemic Drug.

OBJECTIVES: Fenofibric acid (FA) is antihyperlipidemic agent and commercially available as a tablet formulation that weighs 840 mg for 105 mg of active substance. A new formulation with less inactive substance was developed as an alternative to the conventional formulation. The purpose of this study was to evaluate the dissolution and the relative bioavailability of the surface solid dispersion (SSD) and conventional formulations of FA by comparing them with the reference formulation in its commercial tablets. The in vitro-in vivo correlation among these tablet formulations was also evaluated. MATERIALS AND METHODS: The dissolution study was performed in phosphate buffer pH 6.8 and biorelevant fasted state simulated intestinal fluid. Dissolution efficiency and mean dissolution time (MDT) were used to compare the dissolution profiles. The bioavailability study, using nine healthy volunteers, was conducted based on a single-dose, fasted, randomized, crossover design. The in vivo performance was compared using the pharmacokinetic parameters Cmax, Tmax, AUC0-72, and AUC0-∞. A linear correlation model was tested using MDT and mean residence time (MRT). RESULTS: The results indicated that there were significant differences in the dissolution performances but no significant differences among the mean Cmax, Tmax, AUC0-72, or AUC0-∞ estimated from the SSD, conventional, and reference formulations. A poor correlation was found between MRT and MDT of the three formulations. CONCLUSION: The SSD formulation led to an instantaneous dissolution of the drug due to the presence of the polymer and the physical structure of the SSD. The conventional formulation could not achieve rapid dissolution despite its satisfying the requirement for immediate drug release dosage form. Both formulations could be considered bioequivalent with the reference. The in vitro dissolution behavior of FA using a single medium did not reflect their in vivo properties in the fasted condition. There was no correlation between the in vitro dissolution and the in vivo bioavailability of FA in this condition.

Dissolution Profile of Mefenamic Acid Solid Dosage Forms in Two Compendial and Biorelevant (FaSSIF) Media.

Mefenamic acid is a non-steroidal anti-inflammatory drug (NSAID) that is widely used for the treatment of mild-to-moderate pain. Mefenamic acid belongs to the Biopharmaceutical Classification System (BCS) class II drug which has lower water solubility but high permeability. There are two different compendial methods available for dissolution tests of mefenamic acid solid dosage forms, i.e. methods of United States Pharmacopeia 37 (USP) and Pharmacopoeia of the People's Republic of China 2010 (PPRC). Indonesian Pharmacopeia V ed. (FI) adopted the USP method. On the other hand, many researches focused on the use of a 'biorelevant' medium to develop the dissolution test method. The aim of this research was to study the dissolution profile of mefenamic acid from its solid dosage forms (caplet and capsule) available in the Indonesian market with three different dissolution medium: USP, PPRC, and biorelevant fasted simulated small intestinal fluid (FaSSIF) media. The tested products consisted of the innovator's product (available only in caplet dosage form, FN caplet) and generic products (available as caplet and capsule). The dissolution test of the drug products in all dissolution media was performed in 900 mL of medium using apparatus II (paddle) at a temperature of 37°C and rotation speed of 75 rpm, except for the capsule product and for USP medium, both of which tests were done using apparatus I (basket) with rotation speed of 100 rpm. The solubility test of mefenamic acid was carried out in all media at temperature of 37°C. The result obtained from the solubility test showed that the the highest solubility of mefenamic acid was obtained in USP medium (approximately 2 mg/mL), followed by PPRC medium (about 0.5 mg/mL), and FaSSIF medium (approximately 0.06 mg/ml). In the dissolution test, percentage of drug dissolved in in the USP and PPRC media after 45 min for all products reached more than 75%, except for the PN caplet in USP medium which reached only about 44%. Meanwhile, in the biorelevant medium, the percentage of drug dissolved for all products did not exceed 16%. In all dissolution media, the capsule dosage form achieved the highest dissolution rate.