Preparation and Characterization of Fenofibrate-Loaded Nanostructured Lipid Carriers for Oral Bioavailability Enhancement (original) (raw)
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International journal of nanomedicine, 2016
Self-nanoemulsifying drug delivery systems (SNEDDS) have become a popular formulation option as nanocarriers for poorly water-soluble drugs. The objective of this study was to investigate the factor that can influence the design of successful lipid formulation classification system (LFCS) Type III SNEDDS formulation and improve the oral bioavailability (BA) of fenofibrate. LFCS Type III SNEDDS were designed using various oils, water-soluble surfactants, and/or cosolvents (in considering the polarity of the lipids) for the model anticholesterol drug, fenofibrate. The developed SNEDDS were assessed visually and by measurement of the droplet size. Equilibrium solubility of fenofibrate in the SNEDDS was conducted to find out the maximum drug loading. Dynamic dispersion studies were carried out (1/100 dilution) in water to investigate how much drug stays in solution after aqueous dispersion of the formulation. The BA of SNEDDS formulation was evaluated in the rat. The results from the ch...
Pharmaceutical Development and Technology, 2017
The objective of this study was to enhance physiochemical properties as well as oral bioavailability of the poorly water soluble drug fenofibrate (FB), through preparation of amorphous solid dispersions (ASDs). ASDs were prepared via freeze drying using polyvinylpyrrolidone (PVP) K30 and poloxamer 188 as hydrophilic carriers. Formulations were optimized by 3 2 full factorial design (FFD) with PVP−K30 level (X 1) and poloxomer 188 level (X 2) as independent variables and particle size (Y 1), zeta potential (Y 2), drug content (Y 3) and dissolution rate (T90, (Y 4)) as dependent variables. Optimized FB nanoparticles were physicochemically evaluated and formulated into lyophilized sublingual tablets. Pharmacokinetic, pharmacodynamic and histological finding of optimized formulation were performed on rabbits. Y 1 and Y 4 were significantly affected by independent variables while Y 2 and Y 3 were not affected. Physicochemical characterization showed the drug was in amorphous state, nanometer range and pharmacophore of FB was preserved. Administration of optimized FB tablets to rabbits with fatty liver led to significant reduction (P < 0.001) in serum lipids. Moreover, histological analysis of liver specimens confirmed the improved efficacy in animals with fatty liver. In this study, we confirmed that ASDs of FB had beneficial effects on managing fatty liver and serum lipids level in hyperlipidemic rabbits.
Frontiers in Pharmacology
Background: The choice of lipid excipients and their origin are crucial determinant factors in the design of self-nanoemulsifying drug delivery system (SNEDDS). Aim: To investigate the aspects of alternative excipients which can influence the development of efficient SNEDDS and determine the fate of fenofibrate in aqueous media. Methods: SNEDDS of two groups (a and b) were developed using Cremercoor MCT/Capmul MCM and Kollisolv MCT/Imwitor 742 blended oils and water soluble surfactants (to improve lipid polarity) for the model anti-cholesterol drug fenofibrate. Visual assessment was employed and droplet size measurement was taken into initial consideration for optimized SNEDDS. Further SNEDDS optimizations were done on the basis of maximum drug loading by equilibrium solubility studies and maximum solubilized drug upon aqueous dispersion by dynamic dispersion studies. In vitro lipolysis was examined under simulated Fed and Fasted conditions. Intestinal permeability study of the optimal SNEDDS formulation was compared with the raw fenofibrate dispersion using non-everted "intestinal sac technique." Results: Initial characterization and solubility studies showed that mixed glycerides of Kollisolv MCT/Imwitor 742 (group b) containing formulations generated highly efficient SNEDDS as they are stable and produced lower nanodroplets with higher drug loading (group b) as compared to mixed glycerides of Cremercoor MCT/Capmul MCM (group a). In vitro dispersion and digestion studies confirmed that SNEDDS of group b (polar mixed glycerides) can retain high amount of drug (99% drug in solution for more than 24 h time) in dispersion media and have high recovery after digestion. The results from the permeability assessment confirmed that fenofibrate had 4.3-fold increase with F3b SNEDDS compared with the control.
AAPS PharmSciTech, 2012
Lipid-based drug carriers are likely to have influence on bioavailability through enhanced solubilization of the drug in the gastrointestinal tract. The study was designed to investigate the lipid formulation digestibility in the simulated gastro intestinal media. Fenofibrate was formulated in representative Type II, IIIA, IIIB and IV selfemulsifying/microemulsifying lipid delivery systems (SEDDS and SMEDDS designed for oral administration) using various medium-chain glyceride components, non-ionic surfactants and cosolvents as excipients. Soybean oil was used only as an example of long-chain triglycerides to compare the effects of formulation with their counterparts. The formulations were subjected to in vitro digestion specifically to predict the fate of the drug in the gastro intestinal tract after exposure of the formulation to pancreatic enzymes and bile. In vitro digestion experiments were carried out using a pH-stat maintained at pH 7.5 for 30 min using intestinal fluids simulating the fed and fasted states. The digestion rate was faster and almost completed in Type II and IIIA systems. Most of the surfactants used in the studies are digestible. However, the high concentration of surfactant and/or cosolvent used in Type IIIB or IV systems lowered the rate of digestion. The digestion of medium-chain triglycerides was faster than long-chain triglycerides, but kept comparatively less drug in the post digestion products. Medium-chain mixed glycerides are good solvents for fenofibrate as rapidly digested but to improve fenofibrate concentration in post digestion products the use of long-chain mixed glycerides are suggested for further investigations.
2020
Nanostructured lipid carriers (NLCs) are a recent approach for the delivery of poorly soluble drugs with low oral bioavailability. Nanostructured Lipid Carriers (NLCs) are mixture of solid lipids along with irreconcilable liquid lipids. The objective of the current study was to formulate and characterize Nifedipine loaded NLCs coated with Fenugreek Seed Polysaccharide for particle size, entrapment efficiency and in vitro drug release after 24h. NLCs of Nifedipine coated with Fenugreek Seed Polysaccharide were prepared by solvent injection method. A complete 2 factorial design was used for the evaluation of the prepared Nifedipine NLCs. The size and the morphology of the particles in suspension have been determined by electron microscopy studies and in vitro drug release studies by dialysis technique. Optimized formulation display 337nm average particle size and -52.4mV zeta potential that transmit good stability of NLCs dispersion. In vitro release study showed burst release for ini...
Enhancing the Solubility of Fenofibrate by Nanocrystal Formation and Encapsulation
AAPS PharmSciTech, 2017
Development of techniques to enhance bioavailability of drugs having poor water solubility is a big challenge for pharmaceutical industry. Solubility can be enhanced by particle size reduction and encapsulation using hydrophilic polymers. Fenofibrate (FF) is a drug for regulating lipids. Multi-fold enhancement in solubility of FF has been achieved by nanocrystal formation in the present study. Nanoparticles were prepared by an evaporation-assisted solvent-antisolvent interaction (EASAI) approach. Water-soluble polymers, viz. polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA), and hydroxypropyl methylcellulose (HPMC), were used to encapsulate and thus control the particle size of FF nanocrystals. Spherical particles having average particle size well below 30 nm could be prepared under optimum conditions. Almost complete release of the drug molecules from the polymer-stabilized nanocrystals within 2 h was clearly evident from the in vitro drug release studies. Infrared (FTIR) spectro...
Formulation Development and In Vitro Evaluation of Immediate Release Fenofibrate Pellets
2014
The present study was aimed to formulate and evaluate immediate release fenofibrate pellets using pan coater. Fenofibrate, anti lipidemic drug, being water insoluble with a half life of 22.1 h suitable to develop immediate release pellets for the treatment of primary hypercholesterolemia. Eight formulations (F1-F8) of fenofibrate pellets were prepared using a combination of PVPK 30 as binder and starch as a disintegrant. The prepared pellets were subjected to micrometric properties and In vitro drug release studies. The optimized formulation, F8, showed 99.1% drug release in 30 min. Scanning electron microscopy (SEM) studies showed that the prepared pellets are spherical in shape. The release profile for optimized formulation (F8) was comparable and found higher release than the marketed formulation (LIPICARD) for fenofibrate. The mathematical model was built on the hypotheses that drug diffusion and drug dissolution in the release environment are the key phenomena affecting drug re...
Formulation and Evaluation of Fenofibrate-loaded Nanoparticles by Precipitation Method
Indian Journal of Pharmaceutical Sciences, 2018
Shelake, et al.: Fenofibrate-loaded Nanoparticles by Precipitation Method Nanoparticles have applications in the formulation of poorly water soluble drugs to improve their bioavailability. Preparation and evaluation fenofibrate-loaded nanoparticles by precipitation method to enhance solubility and bioavailability was the primary aim of the present investigation. Nano particles of fenofibrate, a BCS class II drug, were prepared by precipitation technique and characterized using Fouriertransform infrared spectroscopy, differential scanning calorimetry, powder X-ray diffraction, scanning electron microscopy, zeta potential and drug release studies in vitro. Data from the differential scanning calorimetry, powder X-ray diffractometry and Fourier-transform infrared spectroscopy showed no interaction between drug and the polymers. Scanning electron microscopy images indicated that nanoparticles were spherical in shape. Water solubility of drug-loaded nanoparticles was increased as compared to the pure drug and showed improved dissolution profile, which indicated that nanoprecipitation was simple and precise. This laboratory scale method as well as this approach could be employed for solubility and bioavailability improvement of BCS class II drugs.
Medical Principles and Practice, 2022
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 were then analyzed using a high-performance liquid chromatography (HPLC) method. Data were statistically analyzed using the analysis of variance (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 fe...
Medical Principles and Practice, 2022
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 an...