Miglyol 812, Tween 80, and Transcutol P were purchased from Prolabo (France). Materialįenofibrate was kindly provided by Galpharma laboratories (Sfax, Tunisia).
#BCS CLASS 4 DRUGS LIST FREE#
Two methods were used to investigate the permeability of the optimized ME across the GI membrane, and the results were compared with those of the free drug powder. The objective of the experimental design is to minimize the droplet size and to maximize the zeta potential using a low concentration of surfactant. The realization of ternary phase diagrams was coupled with the factorial design. The selection of excipients was based on the solubilization capacity of fenofibrate and its permeability improvement across the GI membrane. The main purpose of this study is to enhance the permeability of fenofibrate by formulating a ME for oral administration. It is an efficient method that has been used to optimize the development of ME. The technique of factorial design indicates the relative significance of a number of variables and their interactions. The two approaches require a large number of experiments and, consequently, a lot of work time and a high cost. To formulate a ME, the classical and recognized approaches are phase titration and phase inversion. The reasons may be bio incompatibility, economy, or performance. This can be an interesting strategy to enhance the drug permeability across the gastrointestinal (GI) barrier, where high surfactant levels are often not acceptable. In addition, ME has shown a high solubilization capacity of lipophilic drugs with a droplet size of the order of nm which leads to more efficiency for a large area upon dispersion. To microemulsify the entire oil and water phases, ME requires high surfactant concentrations. The value of the particle surface charges indicates the stability of ME at the macroscopic level. However, in order to provide a very low interfacial tension (≤10 -3 mN/m), the surface charge properties are studied through the zeta potential. These characteristics seem ideal for an oral formulation of a poorly aqueous soluble drug.
They are transparent, isotropic, and thermodynamically stable with a droplet size usually in the range of 20-200 nm. They are systems of water, oil, and surfactant frequently combined with a cosurfactant. Microemulsions (MEs) are a lipid-based formulation. Various formulation strategies have tried to overcome this problem such as solid dispersion, complexations with cyclodextrins, and coprecipitates. This active metabolite presents a poor bioavailability which has been considered as its main drawback. As a prodrug, fenofibrate will be rapidly converted after oral administration by hydrolysis of the ester into an active and major metabolite, the fenofibric acid. It is a lipid-lowering agent used to treat high levels of cholesterol and triglyceride. It is a class II drug according to the Biopharmaceutical Classification System (BCS) since it has a high permeability. Introductionįenofibrate is a poorly water soluble drug, and it is neutral and lipophilic (log ). Thus, this paper shows that the composition and the characteristics of ME may be explored to increase the permeability of fenofibrate across the GI membrane. The use of the excipients that inhibit GI P-glycoprotein may be a new perspective. This suggests that the carrier-mediated uptake/efflux may present the dominant transport mechanism of fenofibrate. The ex vivo technique, performed using the everted gut sac model, showed a 2.5-fold higher permeability. The passive permeability evaluated using Sartorius was 1.6 times higher than that of the free drug. The optimized ME showed a droplet size of 48.5 nm and physical stability. The classical method of ME development was coupled with the factorial design in order to minimize the droplet size using a low concentration of surfactant. A quick selection of excipients was made based on the capacity of solubilization and the value of hydrophilic-lipophilic balance. Its main drawback is the low bioavailability of the metabolite. It undergoes a nearly complete presystemic metabolism. It is a prodrug that is converted rapidly after oral administration into a major active metabolite which is the fenofibric acid. Our work is aimed at exploring the composition and the properties of microemulsion (ME), as a drug delivery system, to enhance the permeability across the gastrointestinal (GI) barrier of fenofibrate, a BCS class II drug.
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