Exploiting itraconazole-loaded nanomixed micelles in coated capsules as efficient colon-targeted delivery system for improved antifungal and potential anticancer efficacy.

Chronic Inflammatory bowel diseases are usually accompanied by opportunistic colonic fungal infections. Itraconazole (ITZ), is a highly lipophilic broad-spectrum antifungal drug that is superiorly effective against several fungal species. Box-Behnken design was adopted to design ITZ-nanomixed micelles (ITZ-NMMs), aiming to enhance ITZ solubility, using various concentrations of Pluronic® L121, Cremophor EL, and with either sodium-deoxycholate or Pluronic® F68 through thin film hydration technique. Optimized formula composed of 90 % Pl-L121, 9.1% Cremophor EL, 3.127 % ITZ concentration and SDC as the hydrophilic surfactant and its particle size, Polydispersity index, zeta potential, entrapment efficiency, and release extent after 3 h were found to be 17.82 ± 0.189 nm, 0.26 ± 0.014, -6.72 ± 0.725 mV, 66 ± 7.4%, and 96.3 ± 7.22%, respectively. In vitro ITZ release study implied the ability of optimal ITZ-NMMs to enhance ITZ solubility in comparison to ITZ suspension. Also, augmented anti-fungal and anti-cancer activities were proven as ITZ-NMMs IC50 was 16.5 times that of pure ITZ. Afterwards, lyophilized optimal ITZ-NMMs formula was loaded into Eudragit S100-coated capsules where in vitro release and in vivo X-ray imaging ensured protection of ITZ release in either the stomach or intestine and targeting it to the colon. Such results suggested promising ITZ-NMMs system, capable of enhancing ITZ solubility in the intended target site, therefore, can be used not only in the treatment of colon fungal infections but also augments colon cancer therapy.

Pharmacokinetic study of an anti-trypanosome agent with different formulations and administration routes in mice by HPLC-MS/MS.

Previously compound 12 showed great anti-trypanosome activity without toxicity in an in vivo study. In the current study, a sensitive and rapid high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed and validated to investigate its pharmacokinetics in mouse plasma. A protein precipitation method was applied to extract the compound, and it was then separated using a Kinetex C18 column with mobile phase consisting of acetonitrile-0.1% formic acid water (50:50, v/v) at a flow rate of 300 µl/min. The analytes were detected with the multiple reaction monitoring in negative electrospray ionization source for quantitative response of the compounds. Compound 12 was detected at m/z 477.0 → 367.2, while the internal standard compound 14 was detected at m/z 499.2 → 268.2. Inter- and intra-day precision was <5.22 and 2.79% respectively, while the accuracy range was within ±9.65%. The method was successfully applied to evaluate the pharmacokinetics of compound 12 in mouse plasma with two formulations (20% Cremophor EL or sesame oil) and drug administration routes (oral and intraperitoneal injection). We observed a better drug serum concentration with the Cremophor formulation, and the two different drug administration routes did not show significant differences from the drug distribution.

In Vitro Effects of Paclitaxel and Cremophor EL on Human Riboflavin Transporter SLC52A2.

Paclitaxel, a mitotic inhibitor with anti-cancer effects, is dissolved in Cremophor EL (CrEL). However, peripheral neuropathy is a known side effect. As one of the mechanisms of the neuropathy, mitochondrial dysfunction has been proposed, while peroxidation products are involved in the cause of CrEL-induced neurotoxicity. Riboflavin is an essential nutrient required for ATP production in mitochondria and has an antioxidant role as a coenzyme for glutathione. Therefore, riboflavin transporters might play a key role to mitigate neuropathy. However, it is unclear whether paclitaxel and CrEL affect these transporters. In this study, human riboflavin transporter SLC52A2 was used to analyze the effects of paclitaxel and CrEL. CrEL, but not paclitaxel, inhibited uptake of riboflavin in human embryonic kidney 293 cells transfected with the SLC52A2 expression vector, suggesting that altered riboflavin disposition may be involved in the pathogenesis of paclitaxel/CrEL toxicity.

Successful switch to oral tacrolimus in a patient with hypersensitivity reaction to parenteral vitamin K, cyclosporine, and tacrolimus: A case report.

INTRODUCTION: Calcineurin inhibitors are widely used for the prevention and treatment of graft versus host disease in patients undergoing allogeneic hematopoietic stem cell transplantation, and successful treatment with calcineurin inhibitors is very important for the management of these cases. CASE REPORT: A 19-year-old man with thalassemia major experienced hypersensitivity reaction to parenteral vitamin K, cyclosporine, and tacrolimus before hematopoietic stem cell transplantation. All three episodes of reaction appeared a few minutes after administration of offended drugs and cause systemic signs and symptoms of anaphylaxis, i.e. itching, flushing, difficulty in breathing, and hypotension. MANAGEMENT AND OUTCOME: Hypersensitivity reaction was fully controlled by immediately discontinuing the drug and administering hydrocortisone, chlorpheniramine, epinephrine, and intravenous fluids. During hospitalization, the patient tolerated oral tacrolimus without any complication. DISCUSSION: It appears that Cremophor EL (polyoxyethylated castor oil) which acts as a carrier, solubilizer, and emulsifier in intravenous calcineurin inhibitors is responsible for the occurrence of anaphylactic reaction (anaphylaxis); therefore, it is suggested that the administration of cremophor-containing drug should be avoided in patients with a previous history of hypersensitivity reaction to one of these drugs.

Potential cross-reactivity of polysorbate 80 and cremophor: A case report.

INTRODUCTION: Anaphylactic and hypersensitivity reactions are known adverse effects of many drug products and may be due to the inactive ingredients of the drug formulation. Specifically for paclitaxel and docetaxel, it is their excipients (cremophor and polysorbate 80, respectively) that have been identified as being most likely responsible for these reactions. CASE REPORT: The patient is a 39-year-old female, with a history of breast cancer and no known allergies, who was scheduled to start chemotherapy. While being administered fosaprepitant, she reported shortness of breath and was noted to be hypotensive and flushed. Two months later, the patient returned to clinic to start weekly paclitaxel. During the administration of the paclitxel test dose, the patient reported difficulty breathing, flushing, and chest tightness. Management and outcome: Both medication reactions were managed with epinephrine and other supportive medications. Fosaprepitant was taken out of the patient's antiemetic regimen for future cycles and paclitaxel was switched to nab-paclitaxel. DISCUSSION: It is well documented that paclitaxel and fosaprepitant have the potential to cause hypersensitivity reactions due to their excipients. While it is likely that each reaction was a unique event, it is difficult to ignore the possibility of cross-reactivity due to the presence of oleic acid in both excipients.

Stability of Chlorophyll a Monomer Incorporated into Cremophor EL Nano-Micelles under Dark and Moderate Light Conditions.

In this paper, stability of chlorophyll a monomers encapsulated into the Cremophor EL nano-micelles was studied under dark and moderate light conditions, typical of a room with natural or artificial lighting, in the presence of oxygen. The pigment stability against visible light was determined using the dynamic light scattering and molecular spectroscopy (UV-Vis absorption and stationary fluorescence) methods. Chlorophyll a, at the molar concentration of 10-5 M, was dissolved in the 5 wt% Cremophor emulsion for comparison in the ethanolic solution. The stability of such a self-assembly pigment-detergent nano-system is important in the light of its application on the commercial-scale. The presented results indicate the high stability of the pigment monomeric molecular organization in the nano-emulsion. During the storage in the dark, the half-lifetime was calculated as about 7 months. Additionally, based on the shape of absorption and fluorescence emission spectra, chlorophyll aggregation in the Cremophor EL aqueous solution along with the time was excluded. Moreover, the average size of detergent micelles as chlorophyll carriers was not affected after 70 days of the nano-system storage. Pigment stability against the moderate white light (0.1 mW) did not differ significantly from storage conditions in the dark. The photooxidation products, detected by occurrence of new absorption and fluorescence emission bands, was estimated on the negligible level. The stability of such a self-assembly pigment-detergent nano-system would potentially broaden the field of chlorophyll a (chl a) application in the food industry, medicine or artificial photosynthesis models.

Submicellar liquid chromatography with fluorescence detection improves the analysis of naproxen in plasma and brain tissue.

Rapid, simple, and sensitive submicellar liquid chromatography with fluorescence detection was developed and validated to quantify naproxen in plasma and brain samples after oral administration of Naproxen formulations. The method used tramadol as an internal standard. Different submicellar mobile phases with organic phases ranging from 40 to 60% were studied to improve the native fluorescence of the Naproxen and decrease retention times. Separation was done in a Zorbax SB C8 column (250 × 4.6 mm, 5 µm) with a mobile phase containing acidic 0.007 M sodium dodecyl sulfate/acetonitrile (50:50, v/v) at a flow rate of 1 mL/min. Detection was performed with an excitation wavelength of 280 nm and emission of 310 nm and 360 nm for internal standard and Naproxen, respectively. The method was validated by International Conference of Harmonization standards. The method is specific, accurate, and precise (relative standard deviation <3%). Limits of detection and quantification were 0.08 and 0.25 µg/mL, respectively, for biological samples. This method was applied to analyze brain/plasma ratios in mice that had received oral administrations of Naproxen micellar formulations containing 10% w/w of sodium dodecyl sulfate, Cremophor RH 40, or Tween 80. The sodium dodecyl sulfate micelles were faster and more widely distributed in the mouse brains.

A rare case of generalized tonic-clonic seizure related to paclitaxel infusion.

WHAT IS KNOWN AND OBJECTIVE: Paclitaxel (Taxol) is an antineoplastic agent approved in the United States for the treatment of lung, breast, cervical, pancreatic cancers and Kaposi sarcoma. Paclitaxel does not cross the blood brain barrier, so central nervous system adverse effects are uncommon. CASE DESCRIPTION: We describe a 60-year-old woman with Stage IIIa squamous cell carcinoma of the left lung, who developed a generalized tonic-clonic seizure during her first infusion of paclitaxel. WHAT IS NEW AND CONCLUSION: Seizure related to a hypersensitivity reaction from paclitaxel infusion are rare but could be life-threatening and require immediate recognition, treatment and exclusion of other possible aetiologies.

Pharmacokinetic modeling of the blood-stable camptothecin analog AR-67 in two different formulations.

AR-67 is a lipophilic camptothecin analog currently under clinical investigation using a Cremophor EL based formulation. However, as potential toxicity limitations exist in the clinical use of Cremophor, an alternative cyclodextrin (SBE-ß-CD) based formulation has been proposed. Pharmacokinetic (PK) studies were conducted in mice and the SBE-ß-CD based formulation was compared with the Cremophor EL formulation. PK studies were conducted following intravenous or oral administration of AR-67 in either Cremophor or SBE-ß-CD formulation in mice. Noncompartmental analysis was used to determine the plasma and tissue drug distribution. A non-linear mixed effects (population) PK model was developed to fit both the oral and intravenous data and to estimate key PK parameters. The effect of formulation was explored as a covariate in the PK model. AR-67 in the SBE-ß-CD formulation had similar plasma PK and biodistribution to that in the Cremophor EL formulation. The proposed two-compartment model described the plasma PK of AR-67 in both formulations adequately. AR-67 in the SBE-ß-CD formulation exhibited dose linearity following both oral and intravenous administration. Our studies indicate that SBE-ß-CD is a viable alternative to Cremophor EL as a pharmaceutical excipient for formulating AR-67.

A Novel Dantrolene Sodium-Loaded Mixed Micelle Containing a Small Amount of Cremophor EL: Characterization, Stability, Safety and Pharmacokinetics.

Dantrolene sodium (DS) is the only drug specifically used for the treatment of malignant hyperthermia. Nevertheless, its clinical application is significantly restricted due to its aqueous insolubility and the limited formulations available in clinical practice. In order to solve these problems, a novel mixed micelle composed of phospholipid and Cremophor EL was designed and evaluated. The mixed micelle was prepared using a stirring- ultrasonic method. The Dynamic Light Scattering (DLS) results showed that the micelle was small in size (12.14 nm) and narrowly distributed (PdI = 0.073). Transmission Electron Microscopy (TEM) images showed that the micelle was homogeneous and spherical. The stability study indicated that the system was stable for storage and dilution with distilled water, while the safety testing showed that the micelle was safe for intravenous administration with low hemolysis rates and low allergic reaction rates. In the pharmaceutics study, the Cmax and AUC0-t of the DS-loaded micelle were 4- and 4.5- folds higher than that of the DS. Therefore, the constructed phospholipid-Cremophor EL mixed micelle is a promising drug delivery system for DS.

Ionic-Liquid-Based Paclitaxel Preparation: A New Potential Formulation for Cancer Treatment.

Paclitaxel (PTX) injection (i.e., Taxol) has been used as an effective chemotherapeutic treatment for various cancers. However, the current Taxol formulation contains Cremophor EL, which causes hypersensitivity reactions during intravenous administration and precipitation by aqueous dilution. This communication reports the preliminary results on the ionic liquid (IL)-based PTX formulations developed to address the aforementioned issues. The formulations were composed of PTX/cholinium amino acid ILs/ethanol/Tween-80/water. A significant enhancement in the solubility of PTX was observed with considerable correlation with the density and viscosity of the ILs, and with the side chain of the amino acids used as anions in the ILs. Moreover, the formulations were stable for up to 3 months. The driving force for the stability of the formulation was hypothesized to be the involvement of different types of interactions between the IL and PTX. In vitro cytotoxicity and antitumor activity of the IL-based formulations were evaluated on HeLa cells. The IL vehicles without PTX were found to be less cytotoxic than Taxol, while both the IL-based PTX formulation and Taxol exhibited similar antitumor activity. Finally, in vitro hypersensitivity reactions were evaluated on THP-1 cells and found to be significantly lower with the IL-based formulation than Taxol. This study demonstrated that specially designed ILs could provide a potentially safer alternative to Cremophor EL as an effective PTX formulation for cancer treatment giving fewer hypersensitivity reactions.

Experience with non-cremophor-based paclitaxel-gemcitabine regimen in advanced pancreatic cancer: Results from a single tertiary cancer centre.

BACKGROUND & OBJECTIVES: Gemcitabine combined with non-cremophor-based paclitaxel is one of the standards of care in advanced inoperable pancreatic cancer. This study was undertaken to retrospectively evaluate real world non-trial outcomes with this combination. METHODS: Patients with histologically proven advanced inoperable pancreatic adenocarcinoma (PDAC), treated with non-cremophor-based paclitaxel-gemcitabine combination (PG) (gemcitabine-nanoxel or gemcitabine-abraxane) between January 2012 and June 2015, were retrospectively analyzed. Response assessment was done every 8-12 wk with computed tomography scan and responses were measured as per the Response Evaluation Criteria in Solid Tumours 1.1 criteria where feasible. Toxicity was recorded as per the Common Terminology Criteria for Adverse Events (CTCAE) v4 criteria. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. RESULTS: A total of 78 patients with PDAC were treated with the combination. Of these, 83.3 per cent of patients had metastatic disease. The median number of chemotherapy cycles administered was three. The objective response rate for the whole group was 30.8 per cent. Grade III/IV toxicities were seen in 35.9 per cent of patients. Median PFS was 5.6 months and median OS was 11.6 months. INTERPRETATION & CONCLUSIONS: Non-cremophor-based paclitaxel in combination with gemcitabine appeared efficacious for advanced pancreatic cancers in routine clinical practice. Within the confines of a single-centre retrospective analysis, gemcitabine-nanoxel and gemcitabine-abraxane appeared to have similar efficacy and toxicity in advanced pancreatic cancers.

Utility of Cremophor RH 40 as a micellar improvement for spectrofluorimetric estimation of sorafenib in pure form, commercial preparation, and human plasma.

An easy, quick, simple and accurate spectrofluorimetric method was recognized and validated for evaluation of sorafenib (SOR) in pure form and biologically in plasma. Cremophor RH 40 (Cr RH 40) used for enhancing the fluorescence activity of SOR in phosphate buffer (pH 7). Cr RH 40 improved the native fluorescence of SOR remarkably in water. The fluorescence spectrum of SOR was observed at 405 nm after excitation at 265 nm. The linearity appeared to be in the range of 5 to 600 ng ml-1 for pure and from 9 to 500 ng ml-1 for plasma using the protein precipitation (ppt) method while from 10 to 500 ng ml-1 for plasma using liquid-liquid extraction method. The precisions and the accuracy of the estimated method gave satisfactory results. The recommended method was effectively applied for determination of SOR in human plasma with high recovery values. The results of some compounds that are possibly found in plasma were studied. The proposed method was also focused on real volunteers and a drug dissolution test.

Preparation and Optimization Lipid Nanocapsules to Enhance the Antitumor Efficacy of Cisplatin in Hepatocellular Carcinoma HepG2 Cells.

This work aimed to develop and optimize several lipid nanocapsule formulations (LNCs) to encapsulate cisplatin (CDDP) for treatment of hepatocellular carcinoma. By comparing the effect of oil/surfactant ratio, lecithin content, and oil/surfactant type on LNC characteristics, two LNCs were selected as optimal formulations: HS15-LNC (Solutol HS 15/MCT/lecithin, 54.5:42.5:3%, w/w) and EL-LNC (Cremophor EL/MCT/lecithin, 54.5:42.5:3%, w/w). Both LNCs could effectively encapsulate CDDP with the encapsulation efficiency of 73.48 and 78.84%. In vitro release study showed that both LNCs could sustain the release CDDP. Moreover, cellular uptake study showed that C6-labeled LNCs could be effectively internalized by HepG2 cells. Cellular cytotoxicity study revealed that both LNCs showed negligible cellular toxicity when their concentrations were below 313 µg/mL. Importantly, CDDP-loaded LNCs exhibited much stronger cell killing potency than free CDDP, with the IC50 values decreased from 17.93 to 3.53 and 5.16 µM after 72-h incubation. In addition, flow cytometric analysis showed that the percentage of apoptotic cells was significantly increased after treatment with LNCs. Therefore, the prepared LNC formulations exhibited promising anti-hepatocarcinoma effect, which could be beneficial to hepatocellular carcinoma therapy.

Safe administration of docetaxel after weekly paclitaxel-induced acute pancreatitis.

Acute pancreatitis is an inflammatory process of the pancreas that can be mild to severe. It requires biochemical or radiologic evidence to establish the diagnosis. Only few chemotherapy agents are directly linked to acute pancreatitis. In this case report, we describe a patient who developed a mild acute pancreatitis on weekly paclitaxel with a positive dechallenge and rechallenge. A 57-year-old woman with advanced ovarian cancer started chemotherapy with carboplatin (AUC 5 every three weeks) and weekly paclitaxel (80 mg/m2 on days 1, 8, and 15). On day 13 of cycle 1, the patient presented with elevated lipase and mild epigastric pain with a suspicion of acute pancreatitis. Because the patient was asymptomatic and pancreatic enzymes decreased on day 16, the third paclitaxel dose was given on day 17 and was followed by another increase of these enzymes. She later received carboplatin and docetaxel without any perturbation of the amylase and lipase. Applying the Naranjo adverse drug reaction probability scale, a score of nine was obtained, indicating a definite association between the administration of paclitaxel and acute pancreatitis. This adverse event could be explained by paclitaxel itself or one of two diluents: cremophor or ethanol. Because paclitaxel is use in many chemotherapy protocols, pharmacists and physicians should be aware of this rare adverse event. Docetaxel administration proved to be safe in this patient without any appearance of pancreatitis signs or symptoms.

Paclitaxel pre-medication: A comparison of two steroid pre-medication protocols.

Purpose To evaluate and compare the rate of hypersensitivity reactions between two low-dose steroid pre-medication regimens for paclitaxel-based treatments. Methods This was a single-center, retrospective, descriptive study, comparing the incidence of hypersensitivity reactions in two different dexamethasone pre-medication regimens that took place between July 2013 to December 2014. Patients who were paclitaxel-naïve with a diagnosis of breast or gynecological cancers were included. Patients in the early termination protocol were pre-medicated with a standard pre-medication regimen and if tolerated with no hypersensitivity reaction occurrence, all pre-medications were discontinued after the first two infusions. Patients in the low-dose steroid continuation protocol were pre-medicated with lower doses of dexamethasone, and if the infusion was tolerated with no hypersensitivity reaction, dexamethasone doses were further reduced after the first two infusions. Results A total of 120 patients were included for data analysis. The hypersensitivity reaction rate in the early termination protocol group was 7% (4 out of 60 patients). The hypersensitivity reaction rate in the low-dose continuation protocol group was 5% (3 out of 60 patients). All hypersensitivity reactions occurred during the first infusion, with no hypersensitivity reactions occurring once the dexamethasone pre-medications were discontinued or dose-reduced. All of the patients who experienced a hypersensitivity reaction were successfully re-challenged with paclitaxel and were able to continue their therapy uninterrupted. Conclusion Discontinuing dexamethasone pre-medication altogether after two uneventful infusions or decreasing the dose of dexamethasone paclitaxel pre-medication are both safe alternatives to high-dose steroid pre-medications recommended in product labeling.

Characterization of ibuprofen microparticle and improvement of the dissolution.

The objective of this study was to prepare ibuprofen (IBP) microparticles by pH-change method and enhance the dissolution rate in vitro. Tween80 and Cremophor RH40 were selected as stabilizers to change the microparticles morphology. The microparticles were evaluated by dissolution profiles and characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (XRD), laser particle size analyzer, scanning electron microscope (SEM) and Fourier transform infrared spectroscopy (FTIR). IBP microparticle prepared with surfactants showed a significant increase in dissolution rate (more than three times within 10 min) and an obvious decrease in mean particle size. The morphology of microparticles was obviously changed. XRD and DSC results revealed that the crystalline state of the untreated IBP and the prepared IBP microparticles were similar. The crystallinity of microparticles produced might be lightly reduced by adding surfactants in preparation process. All results showed that it was useful to prepare high dispersion microparticle by adding surfactants in the preparation process for improving the dissolution.

A synergistic effect of Cremophor and beta glucosylceramide to exert liver and sugar protection.

Many commonly used drugs carry the potential to induce hepatotoxicity, and a large number of foods and beverages induce an increase in blood sugar levels. A change in lifestyle by omitting these compounds is not applicable in many circumstances. ß-Glucosylceramide (GC) is a naturally occurring glycosphingolipid that exerts an effect on the immune system. Cremophor EL (CrEL) is a synthetic, nonionic surfactant that is used as a vehicle for the administration of water-insoluble compounds. The aim of the present study was to determine the synergistic effect of oral administration of the combination of GC and CrEL (GCC) when added to potential toxic substrates or to sugar-enriched compounds. Four groups of mice, treated with PBS, GC, CrEL, or GCC were studied in the concanavalin A immune-mediated hepatitis model, in the acetaminophen (APAP) toxicity model, and as additives to two types of sugar-enriched soda drinks. Both GC and CrEL exerted hepatoprotective effects in the ConA hepatitis and APAP toxicity models. Moreover, in both models, GCC exerted a synergistic effect in ameliorating liver damage as manifested by a significant decrease in the ALT serum levels. When added to two types of sugar-enriched sodas, GCC exerted a synergistic effect in ameliorating the increase in blood sugar levels. GCC exerts synergistic hepatoprotective and glucose-protective effects in models of liver damage and increased serum glucose. GCC can provide liver and sugar protection when co-administered with hepatotoxic drugs or sugar-enriched drinks.

PEGylated Nanoparticles Obtained through Emulsion Polymerization as Paclitaxel Carriers.

Polymer nanoparticles (NPs) represent a promising way to deliver poorly water-soluble anticancer drugs without the use of unwanted excipients, whose presence can be the cause of severe side effects. In this work, a Cremophor-free formulation for paclitaxel (PTX) has been developed by employing PEGylated polymer nanoparticles (NPs) as drug delivery carriers based on modified poly(ε-caprolactone) macromonomers and synthesized through free radical emulsion polymerization. Paclitaxel was loaded in the NPs in a postsynthesis process which allowed to obtain a drug concentration suitable for in vivo use. In vivo experiments on drug biodistribution and therapeutic efficacy show comparable behavior between the NPs and the Cremophor formulation, also showing good tolerability of the new formulation proposed.

Kolliphor surfactants affect solubilization and bioavailability of fenofibrate. Studies of in vitro digestion and absorption in rats.

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.