Developing a cosmetic series: Results from the ESSCA network, 2009-2018.

BACKGROUND: There is considerable variability across European patch test centres as to which allergens are included in local and national cosmetics series. OBJECTIVES: To propose a standardized, evidence-based cosmetic series for Europe based on up-to-date analysis of relevant contact allergens. METHODS: We collated data from the European Surveillance System on Contact Allergies (ESSCA) from 2009 to 2018 to determine which cosmetic allergens produce a high yield of contact allergy. Contact allergens with a prevalence of >0.3% that were considered relevant were included. Rare contact allergens were excluded if deemed no longer relevant or added to a supplemental cosmetic series for further analysis. RESULTS: Sensitization prevalences of 39 cosmetic contact allergens were tabulated. Thirty of these allergens yielded >0.3% positive reactions and are therefore included in our proposed European cosmetic series. Six were considered no longer relevant and therefore excluded. Three were included in a supplementary European cosmetic series. An additional nine allergens were included in either the core or supplemental European cosmetic series following literature review. CONCLUSION: We have derived a potential European cosmetic series based upon the above methods. This will require ongoing investigation based upon the changing exposure profiles of cosmetic allergens as well as new and evolving substances.

Solid self-microemulsifying nutraceutical delivery system for hesperidin using quality by design: assessment of biopharmaceutical attributes and shelf-life.

AIM: The present study endeavours to develop a solid self-microemulsifying nutraceutical drug delivery system for hesperidin (HES) using quality by design (QbD) to improve its biopharmaceutical attributes. METHODS: A 32 full factorial design was employed to study the influence of factors on selected responses. Risk assessment was performed by portraying Ishikawa fishbone diagram and failure mode effect analysis (FMEA). The in vivo antidiabetic study was carried on induced diabetic rats. RESULTS: The optimised liquid SMEDDS-HES (OF) formulation showed emulsification time (Y 1) = 102.5 ± 2.52 s, globule size (Y 2) = 225.2 ± 3.40 nm, polydispersity index (Y 3) = 0.294 ± 0.62, and zeta potential (Y 4) = -25.4 ± 1.74 mV, respectively. The solid SMEDDS-HES (SOF-7) formulation was characterised by FTIR, PXRD, DSC, and SEM. The shelf life of SOF-7 was found to be 32.88 months. The heamatological and histopathological data of diabetic rats showed prominent antidiabetic activity. CONCLUSIONS: The optimised formulation showed improved dissolution, desired stability, and promising antidiabetic activity.

Supersaturable self-microemulsifying drug delivery system enhances dissolution and bioavailability of telmisartan.

To enhance the dissolution and oral bioavailability of telmisartan (TMS), a poorly water-soluble anti-hypertensive drug, a supersaturable self-microemulsifying drug delivery system (SuSMEDDS) was developed. Amorphous alkalinized TMS (AAT) was formulated into a SMEDDS, composed of Capmul® MCM (oil), Cremophor® RH40 (surfactant), and tetraglycol (co-surfactant). Although the SMEDDS was rapidly dissolved (>80% within 5 min) in a limited condition (500 mL, pH 6.8), drug precipitation was observed over time, resulting in a decrease in dissolution levels. The precipitation was due to drug recrystallization, as determined by differential scanning calorimetry and powder X-ray diffraction analyses. Several polymers, including Soluplus® (SOL), were screened as precipitation inhibitors; ultimately, SuSMEDDS-SOL was prepared by admixing SOL and the SMEDDS at a 5:100 (w/w) ratio. SuSMEDDS-SOL was superior in terms of dissolution efficiency (>90% over 2 h) and dissolution-retaining time (no precipitation over 2 h). An in vivo pharmacokinetic study in rats revealed that the oral bioavailability of SuSMEDDS-SOL was 4.8-, 1.3-, and 1.2-fold greater than those of the TMS suspension, AAT solution, and SMEDDS, respectively. Therefore, SuSMEDDS-SOL is a promising candidate to enhance the dissolution and oral bioavailability of TMS.

Visualisation of real-time oral biodistribution of fluorescent labeled self-microemulsifying drug delivery system of olmesartan medoxomil using optical imaging method.

In the present study, the biodistribution of self-microemulsifying drug delivery system of hydrophobic olmesartan medoxomil (OM-SMEDDS) was determined by labeling with a fluorescent dye VivoTag®680 XL and Xenolight® DiR. Labeled OM-SMEDDS and control dye solution administered orally to mice; real-time dynamic biodistributions over 7 h were determined by 2D-fluorescent imaging to verify their anatomic location. Fluorescent Emissions by Vivotag 680® XL and Xenolight® DiR labeled OM-SMEDDS emitted 2 to 24 times stronger emission than control dye administered group. To further confirm the results, organs were removed and examined using the same technique at the end of 7 h. VivoTag®680XL and Xenolight® DiR emitted 4 and 1.7 times stronger emission respectively than control dye administered mice in ex-vivo organ imaging studies. This study showed that OM-SMEDDS can be succesfully labeled with fluorescent dye and tracked with optical imaging method for the visualisation of biodistribution of drugs and is also useful for enhanced bioavailability.

Hydrophobic ion pair loaded self-emulsifying drug delivery system (SEDDS): A novel oral drug delivery approach of cromolyn sodium for management of bronchial asthma.

The aim of the present study is to develop a self-emulsifying drug delivery system (SEDDS) for the hydrophobic ion pair (HIP) complex of cromolyn sodium (CS), in order to enhance its intestinal absorption and biological activity. Two ion pairing agents (IPAs) were investigated: hexadecyl pyridininum chloride (HPC) and myristyl trimethyl ammonium bromide (MTAB). The optimum binding efficiency for complexation between investigated IPAs and CS was observed at a molar ratio of 1.5:1, where CS binding efficiency was found to be 76.10 ± 2.12 and 91.37 ± 1.73% for MTAB and HPC, respectively. The two prepared complexes exhibited a significant increase in partition coefficient indicating increased lipophilicity. The optimized CS-HIP complex was incorporated into SEDDS formulations. SEDDS formulations F2 (40% oleic acid, 40% BrijTM98, 20% propylene glycol) and F3 (25% oleic acid, 50% BrijTM98, 25% propylene glycol) exhibited nanometric droplet diameters with monodisperse distribution and nearly neutral zeta potential values. Ex vivo intestinal permeation study, using the non-everted gut sac technique, revealed a significantly higher cumulative amount of permeated drug, after 2 h, for F2 and F3 (53.836 and 77.617 µg/cm2, respectively) compared to 8.649 µg/cm2 for plain CS solution. The in vivo evaluation of plain CS solution compared to F2 and F3 was conducted in an ovalbumin sensitization-induced bronchial asthma rat model. Lung function parameters (tidal volume and peak expiratory flow), biochemical parameters (interleukin-5, immunoglobulin-E, myeloperoxidase and airway remodelling parameters) were assessed in addition to histopathological examination. The results indicated the superiority of F3 followed by F2 compared to plain CS solution for prophylaxis of bronchial asthma in rats.

Abomasal infusion of an exogenous emulsifier improves fatty acid digestibility and milk fat yield of lactating dairy cows.

The objective of our study was to determine the effects of abomasal infusion of an emulsifier on fatty acid (FA) digestibility and production responses of lactating dairy cows. Eight rumen-cannulated cows (109 ± 18 d in milk) were randomly assigned to a treatment sequence in replicated 4 × 4 Latin squares with 18-d periods including 7 d of washout and 11 d of infusion with sampling on the last 4 d. Treatments were abomasal infusions of water carrier only (CON) and 3 levels of increasing doses of Tween 80 (polysorbate 80, Tween 80, Sigma-Aldrich, St. Louis, MO) delivering 15 (D-15), 30 (D-30), and 45 (D-45) g/d. The Tween 80 was dissolved in water before infusions, which were delivered at 6-h intervals. Cows were fed the same diet, which contained (% dry matter) 31% neutral detergent fiber, 17% crude protein, 25% starch, and 4% FA (2% dry matter from a saturated fat supplement containing 33% C16:0 and 51% C18:0). Increasing emulsifier infusion dose quadratically increased digestibility of total FA (60.7, 65.3, 70.9, and 66.8%), 16-carbon FA (61.7, 63.9, 70.4, and 66.7%), and 18-carbon FA (59.8, 65.6, 71.1, and 66.6%, respectively). Increasing emulsifier infusion dose quadratically increased absorbed total FA (625, 670, 744, and 658 g/d), 16-carbon FA (151, 157, 197, and 157 g/d, quadratic), and 18-carbon FA (420, 460, 500, and 444 g/d). Increasing emulsifier infusion dose tended to quadratically decrease dry matter intake (29.0, 28.8, 29.6, and 27.6 kg/d). Increasing emulsifier infusion dose quadratically increased milk fat content (3.23, 3.35, 3.45, and 3.35%), milk fat yield (1.54, 1.61, 1.65, and 1.55 kg/d), ECM (45.7, 46.9, 47.5, and 45.3 kg/d), and plasma nonesterified fatty acid concentration (95.6, 98.4, 101.2, and 98.6 µEq/L). On a yield basis, we observed that de novo, mixed, and preformed FA responded quadratically to Tween 80 infusion due to FA yield increasing up to D-30. Treatments had no effect on milk yield (47.9, 48.3, 48.0, and 46.6 kg/d). In conclusion, short-term infusion of an exogenous emulsifier improved FA digestibility and milk fat yield responses when cows were fed a diet containing a saturated fat supplement. Most digestion and production measurements responded quadratically because the highest dose of exogenous emulsifier (45 g/d) decreased dry matter intake and performance.

In-situ Intestinal Absorption and Pharmacokinetic Investigations of Carvedilol Loaded Supersaturated Self-emulsifying Drug System.

BACKGROUND: Carvedilol (CD), a non-selective beta-blocker, is indicated for the management of mild to moderate congestive heart failure. After oral administration, CD is rapidly absorbed with an absolute bioavailability of 18-25% because of low solubility and extensive first-pass metabolism. OBJECTIVE: The present investigation focused on enhanced oral delivery of CD using supersaturated self-emulsifying drug delivery (SEDDS) system. METHODS: Optimized SEDDS consisted of a blend of Oleic acid and Labrafil-M2125 as an oil-phase, Cremophor-RH40, polyethylene glycol-400 and HPMC-E5 as a surfactant, co-surfactant and supersaturation promoter respectively. Formulations were characterized for physical characteristics, invitro release in simulated and biorelevant dissolution media, intestinal permeability and bioavailability studies in Wistar rats. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analysis, scanning electron microscopy (SEM) studies were used to confirm the crystalline nature and shape of the optimized formulation. RESULTS: DSC and XRD, SEM studies showed that the drug was in amorphous form, and droplets were spherical in shape. Dissolution studies clearly showed distinct CD release in compendial and biorelevant dissolution media. The results from permeability and in-vivo studies depicted 2.2-folds and 3.2-folds increase in permeability and bioavailability, respectively from supersaturated SEDDS in comparison with control. CONCLUSION: The results conclusively confirmed that the SEDDS formulation could be considered as a new alternative delivery vehicle for the oral supply of CD. Lay Summary: Carvedilol (CD) is a non-selective antihypertensive drug with poor oral bioavailability. Previously, various lipid delivery systems were reported with enhanced oral delivery. We developed suprsaturable SEDDS formulation with immediate onset of action. SEDDS formulation was developed and optimized as per the established protocols. The optimized SEDDS formulation was stable over three months and converted to solid and supersaturated SEDDS. The results from permeability and in-vivo studies demonstrated an enhancement in permeability and bioavailability from supersaturated SEDDS in comparison with control. The results conclusively confirmed that the SEDDS formulation could be considered as a new alternative delivery vehicle for the oral administration of CD.

Improved Oral Pharmacokinetics of Pentoxifylline with Palm Oil and Capmul® MCM Containing Self-Nano-Emulsifying Drug Delivery System.

Pentoxifylline (PTX), an anti-hemorrhage drug used in the treatment of intermittent claudication, is extensively metabolized by the liver resulting in a reduction of the therapeutic levels within a short duration of time. Self-nano-emulsifying drug delivery system (SNEDDS) is well reported to enhance the bio-absorption of drugs by forming nano-sized globules upon contact with the biological fluids after oral administration. The present study aimed to formulate, characterize, and improve the oral bioavailability of PTX using SNEDDS. The formulated SNEDDS consisted of palm oil, Capmul® MCM, and Tween® 80 as oil, surfactant, and co-surfactant, respectively. The mixture design module under the umbrella of the design of experiments was used for the optimization of SNEDDS. The dynamic light-scattering technique was used to confirm the formation of nanoemulsion based on the globule size, in addition to the turbidity measurements. In vivo bioavailability studies were carried out on male Wistar rats. The pharmacokinetic parameters upon oral administration were calculated using the GastroPlus software. The optimized SNEDDS had a mean globule size of 165 nm with minimal turbidity in an aqueous medium. Bioavailability of PTX increased 1.5-folds (AUC = 1013.30 ng h/mL) as SNEDDS than the pure drug with an AUC of 673.10 ng h/mL. In conclusion, SNEDDS was seen to enhance the bioavailability of PTX and can be explored to effectively control the incidents of intermittent claudication.

Accelerate development of topical cream drug product using a common platform base formulation.

The aim of this work was to identify stable topical platform cream formulations (placebo creams without active drug substance) using the quality attributes of cream consistency, droplet size distribution (<1 µm), and separation or instability index of <0.1 to accelerate the development of topical cream drug product. The formulations were developed with six emulsifier systems that were screened in three different solvent systems across a range of emulsifier ratios. Each formulation was characterized by microscopy, separation index, and consistency. The results showed that there are three emulsifier combination (PEG 40 stearate:GMS, S21:S2, and PEG 40 stearate:Span 60) that works well with the solvent systems. Platform cream formulations F4, F15, F33, F40, F52, F69, F77, F87, and F106 were found to meet the three criteria for a long-term stable platform cream formulation. Formulation development for topical administered drug product can be very time consuming, expensive, and resourceful in identifying a chemically and physically stable product. In early development, where it can take 1-2 years to develop a first time in human (FTIH) formulation for a new chemical entity. The use of the platform base cream formulations will expedite the early development timeline for new chemical entity by 3-6 months.

The effect of medium chain and long chain triglycerides incorporated in self-nano emulsifying drug delivery systems on oral absorption of cannabinoids in rats.

The aim of this research was to investigate the effect of the lipid component in self-emulsifying drug delivery systems on the oral absorption of major cannabinoids Δ9-tetrahydrocannabinol (THC) and Cannabidiol (CBD). The investigated lipids were either long chain triglycerides (LCT) or medium chain triglycerides (MCT) with different composition, fatty acid chain length, degree of saturation and their absorption pathway to the systemic circulation. Formulations were developed with the purpose of creating thermodynamically stable oil-in-water nano emulsions/suspensions with particle size of 50 nm or less which carry the lipophilic drug and increase water solubility. Following a methodic screening of suitable excipients in-vitro, leading formulations based on sesame oil or MIGLYOL® 812N (Type I LCT/MCT SNEDDS) and cocoa butter or tricaprin (Type II LCT/MCT SNEDDS) were investigated in the freely moving rat model. Results in rat model demonstrated that the effect of each type of lipid on bioavailability of cannabinoids is not straightforwardly anticipated. The differences in the effect of LCT and MCT on absorption was not substantial for Type I formulations, however, more prominent for Type II formulations. This unpredictable behavior in-vivo demonstrates the importance of investigating each vehicle pre-clinically, following the in-vitro development.

Benznidazole self-emulsifying delivery system: A novel alternative dosage form for Chagas disease treatment.

Benznidazole (BZ) tablets are a unique form of treatment available for treating Chagas disease. Development of a liquid formulation containing BZ easy to administer orally for the treatment of paediatric patients, particularly for newborns is urgently required, with the same efficacy, safety and suitable biopharmaceutical properties as BZ tablets. Self-emulsifying drug delivery systems (SEDDS) may improve bioavailability of drugs such as BZ, which have poor water solubility and low permeability. In this context, the aim of this work was to develop a liquid BZ-SEDDS formulation as an alternative to tablets and to evaluate its cytotoxicity in different host cell lines and its efficacy in experimental Trypanosoma cruzi infection in mice. The optimized SEDDS formulation (25 mg/ml of BZ) induced no cytotoxicity in H9c2, HepG2 and Caco2 cells in vitro at 25 µM level. BZ-SEDDS and free-BZ showed similar in vitro trypanocidal activity in H9c2 cells infected by T. cruzi Y strain, with IC50 values of 2.10 ± 0.41 µM and 1.29 ± 0.01 µM for BZ and BZ-SEDDS, respectively. A follow up of efficacy in an acute model of infected mice resulted in the same percentage of cure (57%) for both free-BZ and BZ-SEDDS- groups according to established parameters. Furthermore, no additional in vivo toxicity was observed in animals treated with BZ-SEDDS. Taken together, in vitro and in vivo data of BZ-SEDDS showed that the incorporation of BZ into SEDDS does not alter its potency, efficacy and safety. Thus, BZ-SEDDS can be a more practical and personalized orally administered liquid dosage form compared to suspension of crushed BZ-tablets to treat newborn and young children by emulsifying SEDDS in different aqueous liquids with advantage of dosing flexibility.

In vitro digestibility and bioaccessibility of lipid-based delivery systems obtained via enzymatic glycerolysis: a case study of rosemary extract bioaccessibility.

This work studies the effect of enzymatic glycerolysis on digestibility and bioaccessibility of ratfish liver oil (RLO) rich in alkylglycerols (AKGs), as well as the capability of the glycerolysis product (GP) to act as lipid-based delivery system (LBDS) for a supercritical rosemary extract. For comparison purposes, digestibility and bioaccessibility of two additional lipid systems i.e. original RLO and RLO with addition of GRAS monoolein (MO) as emulsifier agent (RLO + MO), have been evaluated. We have studied the efficiency of the GP and RLO + MO lipid systems as LBDS by combining them with a supercritical rosemary extract (RE), i.e. RE lipid-based formulations. In vitro digestibility and bioaccessibility of un-loaded lipid systems, RE lipid-based formulations and un-carried RE have been determined. The results show a higher digestibility and bioaccessibility of the GP as compared to those of original RLO and RLO + MO. Likewise, a substantial improvement of RE bioaccessibility has been observed when GP is used as lipid carrier of RE. The present work demonstrates that enzymatic glycerolysis is an efficient strategy to obtain highly bioaccessible and potentially bioactive alkylglycerol-based delivery systems, which can be used to increase the bioaccessibility of low water-soluble bioactive compounds.

Glycerin Monostearate Aggravates Male Reproductive Toxicity Caused by Di(2-ethylhexyl) Phthalate in Rats.

Human beings are increasingly exposed to phthalates, which are a group of chemicals used to make plastics more flexible and harder to break, and simultaneously ingesting abundant food emulsifiers via daily diet. The purpose of this study was to investigate the effect of the food emulsifier glycerin monostearate (GMS) on male reproductive toxicity caused by di(2-ethylhexyl) phthalate (DEHP, one of the phthalates) and explore the underlying mechanism. Thirty male Sprague-Dawley rats were randomly divided into control group, DEHP group and DEHP+GMS group. Rats in the DEHP group and DEHP+GMS group were orally administered with 200 mg/kg/d DEHP with or without 20 mg/kg/d GMS. After 30 days of continuous intervention, it was found that the serum testosterone level was significantly lowered in DEHP group and DEHP+GMS group than that in control group (P<0.01). The serum testosterone level and the relative testis weight were significantly decreased in the DEHP+GMS group as compared with those in the DEHP group and control group (P<0.05). More spermatids were observed to be shed off in DEHP+GMS group than in DEHP group. The expression levels of cell cycle checkpoint kinase 1 (Chk1), cell division cycle gene 2 (Cdc2), and cyclin-dependent kinase 2 (CDK2) were down-regulated in DEHP group, and this tendency was more significant in DEHP+GMS group (P<0.05 or P<0.01). There was no significant difference in the P-glycoprotein (P-gp) expression between DEHP group and control group. However, P-gp was markedly down-regulated in DEHP+GMS group (P<0.01). The results indicated that the food emulsifier GMS aggravated the toxicity of DEHP on male reproduction by inhibiting the cell cycle of testicular cells and the expression of P-gp in testis tissues.

Preparation of Calcipotriol Emulsion Using Bacterial Exopolysaccharides as Emulsifier for Percutaneous Treatment of Psoriasis Vulgaris.

An exopolysaccharides/calcipotriol (EPS/CPT) emulsion was prepared using bacterial EPS as emulsifier, sunflower oil as an oil phase and CPT as the loaded drug, and the effect of this emulsion on psoriasis vulgaris treatment was evaluated. An EPS composed of mannose (70.56%) and glucose (29.44%) was obtained from the marine mangrove bacteria Bacillus amyloliquefaciens ZWJ (Zhu Wenjing) strain. The EPS has significant emulsifying activity at the concentration of 1.5%. The prepared EPS/CPT emulsion has small and stable particle size, with a drug content of 0.00492%, and good spreading properties. The in vitro drug release results revealed that the emulsion showed a certain sustained release effect. In vitro and in vivo animal experiments show that the EPS/CPT emulsion can effectively treat psoriasis vulgaris by increasing the accumulation of CPT in psoriatic skin lesions and reducing the levels of inflammatory cells and inflammatory factors (TNF and IL6). Additionally, it has a certain effect on reducing the side effects associated with CPT. This study lays a foundation for the research of EPS in the topical application of medical materials and treatment of psoriasis.

Effects of different emulsifiers on growth performance, nutrient digestibility, and digestive enzyme activity in weanling pigs1.

The objective of this study was to investigate the effects of diets supplemented with sodium stearoyl-2-lactylate (SSL), polyglycerol fatty acid ester (PGFE), and combined emulsifiers (0.02% SSL and 0.08% PGFE) on growth performance, nutrient digestibility, and plasma lipid profiles in weaned piglets and to further evaluate the possible effects of feeding exogenous emulsifiers on digestive enzyme activities and liver bile acid (BA) metabolism. Twenty-eight barrows (age at 35 d, Duroc × Landrace × Yorkshire) with an initial BW of 10.13 ± 0.16 kg were randomly assigned to 4 dietary treatment groups (7 pigs/treatment). Dietary treatment groups included the following: 1) basal diet (Control, CTR); 2) basal diet with 0.1% SSL (SSL); 3) basal diet with 0.1% PGFE (PGFE); and 4) basal diet with 0.08% PGFE+0.02% SSL (PG-SL). SSL diet increased ADG and ADFI of piglets during day 0 to 17 (P < 0.05) compared with the CTR treatment. Piglets fed emulsifier diets experienced a significant improvement in the digestibility of nutrients (DM, CP, ether extract, energy, calcium, and phosphorus) during the first 17 d (P < 0.05). The level of low-density lipoprotein cholesterol (LDL-C) was lower in the PGFE and PG-SL treatment groups than in the CTR treatment group (P < 0.05). Feeding emulsifier diets increased the lipase activity of the pancreas when compared with the CTR diet (P < 0.05). Moreover, the emulsifier diets significantly increased the mRNA expression of FXR (P < 0.05) and decreased the mRNA expression of CYP27A1 (P < 0.05) in the liver. In conclusion, the addition of emulsifiers improved nutrient digestibility and increased the mRNA expression of FXR BA receptors while inhibiting the mRNA expression of BA biosynthesis by CYP27A1 in weanling piglets.

A Novel Self-Emulsifying Drug Delivery System (SEDDS) Based on VESIsorb® Formulation Technology Improving the Oral Bioavailability of Cannabidiol in Healthy Subjects.

Cannabidiol (CBD), a phytocannabinoid compound of Cannabis sativa, shows limited oral bioavailability due to its lipophilicity and extensive first-pass metabolism. CBD is also known for its high intra- and inter-subject absorption variability in humans. To overcome these limitations a novel self-emulsifying drug delivery system (SEDDS) based on VESIsorb® formulation technology incorporating CBD, as Hemp-Extract, was developed (SEDDS-CBD). The study objective was to evaluate the pharmacokinetic profile of SEDDS-CBD in a randomized, double-blind, cross-over design in 16 healthy volunteers under fasted conditions. As reference formulation, the same Hemp-Extract diluted with medium-chain triglycerides (MCT-CBD) was used. CBD dose was standardized to 25 mg. Pharmacokinetic parameters were analyzed from individual concentration-time curves. Single oral administration of SEDDS-CBD led to a 4.4-fold higher Cmax and a 2.85-/1.70-fold higher AUC0-8h/AUC0-24h compared to the reference formulation. Tmax was substantially shorter for SEDDS-CBD (1.0 h) compared to MCT-CBD (3.0 h). Subgroup analysis demonstrated a higher bioavailability in women compared to men. This difference was seen for MCT-CBD while SEDDS-CBD mitigated this gender effect. Overall, SEDDS-CBD showed a significant improvement for all determined pharmacokinetic parameters: increased CBD plasma values (Cmax), favorably enhanced bioavailability (AUC) and fast absorption (Tmax). No safety concerns were noted following either administration.

Investigation of Controlled Release Molecular Mechanism of Oil Phase in Spilanthol Emulsion: Development and In Vitro, In Vivo Characterization.

The aim of the present study was to develop a spilanthol emulsion and investigate the effect of oil and drug physicochemical properties on drug release and skin retention at molecular level. Formulation factors including oil, emulsifier, and humectant were investigated by in vitro skin retention/permeation study and the optimized formulation was evaluated in vitro and in vivo. In addition, the controlled release effect of oil was characterized using drug emulsion distribution study, drug release study, FT-IR, and molecular modeling. The optimized emulsion (squalane as oil phase) obtained the maximum skin retention (118.71 ± 10.30 µg/g), which significantly restored skin hydroxyproline content (23.99 ± 2.21 µg/g), compared with the positive group (14.75 ± 1.84 µg/g) and the negative group (15.55 ± 2.03 µg/g). It was caused by high drug release of squalene and good drug-skin miscibility. FT-IR and molecular modeling showed that spilanthol (SPI) interacted with squalene through Van der Waals force, which was weaker than a hydrogen bond formed with other oils, thus exhibited good drug release properties. And the released drug was stored in the skin due to good drug-skin miscibility, which was proved by miscibility calculation and molecular modeling. In conclusion, an effective emulsion was developed and the controlled release effect of oil phase was proved through drug-excipient interaction.

Cytotoxicity of lecithin-based nanoemulsions on human skin cells and ex vivo skin permeation: Comparison to conventional surfactant types.

As constituents of cellular membranes, lecithins feature high biocompatibility and great emulsifying properties due to their amphiphilicity. Additionally, there are expectations that these naturally occurring emulsifying agents can replace other skin damaging emulsifiers like sodium dodecyl sulfate or sodium laureth sulfate. However, cytotoxicity data of lecithin-based formulations on primary human skin cells are scarce. Thus, we developed nanoemulsions with different kinds of surfactants (amphoteric, anionic and non-ionic), studied the skin permeation of a model drug from this formulations employing Franz-type diffusion cells and monitored their cytotoxicity potential on primary human keratinocytes and fibroblasts using a cell proliferation assay. The skin diffusion studies demonstrated that the amphoteric lecithin-based emulsifiers were superior to non-ionic surfactants in terms of skin permeation, but inferior to anionic emulsifiers. Further, we found that the nanoemulsions containing the amphoteric lecithins as emulsifying agents lead to significantly higher viability rates of both epidermal keratinocytes and dermal fibroblasts than the investigated anionic and non-ionic surfactants. This renders them a promising alternative to conventional emulsifiers used in daily products.

Effects of fat type and emulsifier in feed on growth performance, slaughter traits, and lipid metabolism of Cherry Valley ducks.

A 2-factor test design was used to investigate the effect of an emulsifier (Aldo®, Lonza, America) (200 g/t) in the diet of Cherry Valley meat ducks to replace some of 2 different oils (animal fat and vegetable oil) on meat production performance, slaughter traits, and fat metabolism. The 900 healthy 18-day-old ducks were grouped into 6 treatments, each with 5 replicates and 30 meat ducks per replicate. The 2 fat sources were established as a positive control group, a negative control group (positive control group-some oil (equivalent to metabolic energy of 50 kcal/ton)), and an emulsifier group (negative control group + 200 g/ton Aldo). The results showed that addition of different fat sources in feed had no significant effect on growth performance, carcass properties, and fat metabolism of 18- to 42-day-old meat ducks (P > 0.05). Reducing the amount of oil used in the feed lowered the growth performance, carcass properties, and affected fat metabolism of meat ducks. However, in feeds with 2 fat sources, some oils were replaced by adding Aldo without affecting growth performance and carcass properties of meat ducks, and improved their fat metabolism, reduced triglycerides (TG) in serum, and increased activity of lipoprotein and hepatic lipases in liver and of pancreatic lipase. Thus, addition of Aldo to a low fat diet could improve growth performance, carcass quality, and lipid metabolism, and promote digestion and absorption of fat for meat ducks.