Kolliphor Surfactants Affect Solubilization and Bioavailability of Fenofibrate. Studies of in Vitro Digestion and Absorption in Rats

Abstract

Selection of excipients for drug formulations requires both intellectual and experimental considerations as many of the used excipients are affected by physiological factors, e.g., they may be digested by pancreatic enzymes in the gastrointestinal tract. In the present paper we have looked systematically into the differences between Kolliphor ELP, EL, and RH40 and how they affect the bioavailability of fenofibrate, through pharmacokinetic studies in rats and in vitro lipolysis studies. The study design was made as simple as possible to avoid confounding factors, for which reason the tested formulations only comprised an aqueous micellar solution of the model drug (fenofibrate) in varying concentrations (2-25% (w/v)) of the three tested surfactants. Increased concentrations of Kolliphor ELP and EL led to increased fenofibrate AUC0-24h values. For the Kolliphor RH40 formulations, an apparent fenofibrate absorption optimum was seen at 15% (w/v) surfactant, displaying both the highest AUC0-24h and Cmax. The reduced absorption of fenofibrate from the formulation containing the highest level of surfactant (25% w/v) was thought to be caused by some degree of trapping within Kolliphor RH40 micelles. In vitro, Kolliphor ELP and EL were found to be more prone to digestion than Kolliphor RH40, though not affecting the in vivo results. The highest fenofibrate bioavailability was attained from formulations with high Kolliphor ELP/EL levels (25% (w/v)), indicating that these surfactants are the better choice for solubilizing fenofibrate in order to increase the absorption upon oral administration. Due to drug dependent effects of the different types of Kolliphor, more studies are recommended in order to understand which type of Kolliphor is best suited for a given drug.

Divergent responsiveness of two isoforms of the estrogen receptor to mixtures of contaminants of emerging concern in four vertebrates

“…We previously observed similar hyperstimulation of Esrs with a single compound of selective‐agonists such as Esr1‐agonist 4,4,4′‐(4‐propyl‐[1H]‐pyrazole‐1,3,5‐triyl)trisphenol and Esr2‐agonist 2,3‐bis(4‐hydroxyphenyl)‐propionitrile (Kohno et al, ). However, hyperstimulation by CECs might be due to alteration of membrane permeability of E 1 via NP exposure, which is a non‐ionic surfactant and may affect solubilization and bioavailability of contaminants including E 1 (Berthelsen et al, ). NP exhibited a 0.0036 EEQ following a 2 weeks in vivo exposure based on vitellogenin inductions in fathead minnows, and mixture of estrogenic contaminants with NP followed the pharmacological concept of concentration addition (i.e., an additive effect) (Brian et al, ).…”

“…In contrast to the observed lowest sensitivity of fathead minnows to AG and UB CEC mixtures, the 100× AG and UB CEC mixtures did stimulated fathead minnow Esr1 at 110% ± 3.4 and 142% ± 2.7 (7.9 ± 0.8 and 10. (Berthelsen et al, 2015). NP exhibited a 0.0036 EEQ following a 2 weeks in vivo exposure based on vitellogenin inductions in fathead minnows, and mixture of estrogenic contaminants with NP followed the pharmacological concept of concentration addition (i.e., an additive effect) (Brian et al, 2005).…”

Determination of Acoustical Parameters of Aqueous Solution of Kolliphors Binary Mixtures Using Density, Speed of Sound, Viscosity, and Surface Tension Measurements

“…Moreover, some aqueous solutions with nonionic surfactants can be applied in extraction processes being of significant importance in biotechnological product purification (Ingram et al, ; Lam et al, ). In pharmacy, nonionic Kolliphors (known before as Cremophors) find application in lipid‐based delivery aimed at improving poorly water‐soluble drugs (Berthelsen et al, ; Gelderblom et al, ). The triricinoleate ester of ethoxylated glycerol is the main constituent of Kolliphors.…”

“…find application in lipid-based delivery aimed at improving poorly water-soluble drugs (Berthelsen et al, 2015;Gelderblom et al, 2001). The triricinoleate ester of ethoxylated glycerol is the main constituent of Kolliphors.…”

Rhamnogalacturonan-I Based Microcapsules for Targeted Drug Release

“…The pancreatic extract suspension was prepared as described previously [21]. The composition of the SIF medium is given in Table 1 [22, 23]. During the lipolysis, the pH was maintained at 6.5 by automatic addition of 0.2 M NaOH solution.…”