CAPRYLIC/CAPRIC TRIGLYCERIDE

Transdermal administration of raloxifene hydrochloride (RLX)-loaded nanostructured lipid carriers (NLCs) has been proposed to circumvent its low oral bioavailability (2%). Preformulation studies were carried out to evaluate drug-excipient compatibility of various adjuvants commonly used for NLC preparation (waxes, cholesterol, compritol, gelucire, span 60, span 80, span 85, tween 80, poloxamer 188, oleic acid, caprylic/capric triglyceride, and castor oil). It was used differential scanning calorimetry (DSC), isothermal stress testing (IST), and solubility studies. The most promising excipients were chosen for NLC obtention, and full characterization was done, including in vitro skin permeation. DSC curves suggested drug-excipient interaction among some compounds, and the IST study showed incompatibility of RLX with waxes, compritol, cholesterol, span 60, and poloxamer 188. Solubility studies helped select gelucire, caprylic/capric triglyceride, span 80, and tween 80 for NLC production. Twelve NLCs were obtained (NLC1 to NLC12), but NLC7 and NLC8 were the most promising ones. In vitro release studies demonstrated that NLC7 and NLC8 were able to control RLX release (14.74 and 9.07% at 24 h, respectively) compared with the unloaded drug (> 90% at 24 h). Unloaded RLX did not permeate the diffusion cells' receptor medium and showed higher drug skin retention (11-fold) than RLX-loaded NLC. NLC reduced RLX skin retention, favoring drug permeation to deeper skin layers. NLC7 increased drug flux is 2.4-fold. NLC7 is a promising formulation for RLX transdermal drug delivery.

The targeted delivery of a hydrophilic Tripeptide-3 to the skin using microemulsions or nanoemulsions for facial oil reduction was the focus of this study. The impact factors affecting oil/water transparent dispersion formation, such as the surfactant system, HLB value, and co-solvent, were identified through the water titration method and pseudoternary phase diagram plots. The interfacial tension between caprylic/capric triglyceride (CCT oil) and water was significantly reduced by the surfactant/co-surfactant combination (S mix ) of Cremophore ® RH40 and a double-tails co-surfactant, polyglycerol-3-diisostearate, at an HLB of 13 together with a water-to-co-solvent (PG) ratio of 1:1. A two-level full factorial design of experiment (FFD-DoE) emphasized the independent variables of the HLB value, co-solvent, and CCT oil contents affecting the optimal compositions for micro- or nanoemulsion formation. The low-energy spontaneous emulsification of the optimized combination at a low S mix content (10%) yielded the translucent oil-in-water Tripeptide-3 nanoemulsions with an internal droplet size of 25.7 ± 1.20 nm, a narrow polydispersity index of 0.237 ± 0.129, and 70.6 ± 0.58% transmittance. The in vitro skin permeation study revealed a significantly higher skin penetration and retention of the Tripeptide-3 nanoemulsions compared to the high surfactant microemulsions and coarse emulsions. Skin irritation and oil control efficacy were evaluated in healthy volunteers before and after product application for 28 days. The obtained nanoemulsions not only decreased sebum production but also enhanced skin moisture levels. In conclusion, the meticulously designed nanoemulsions, incorporating suitable excipients, show a promising delivery system for hydrophilic peptides to control sebum overproduction in oily facial skin.

Disruption of the protective stratum corneum barrier increases the skin's vulnerability to microorganisms and facilitates conditions such as dandruff. Dandruff is a disorder of the scalp that causes increased scaling of the SC and is associated with Malassezia fungus. Consequently, many anti-dandruff commercial products use anti-fungal active ingredients such as piroctone olamine also known as Octopirox (OPX). OPX is an active ingredient used in a number of topical preparations for the management of dandruff. The characterization of the physicochemical properties of OPX was previously reported. The aim of the present work was to investigate a range of solvent systems for their effects on OPX interaction with human skin. The solvents used in this study were propylene glycol (PG), diethylene glycol monoethyl ether or Transcutol® (TC), PG monolaurate (PGML), isopropyl myristate (IPM), caprylic/capric triglyceride or Labrafac™ Lipophile WL 1349 (LAB), PG caprylate or Capryol® 90 (CAP), isostearyl isostearate (ISIS) and Plurol® Oleique CC 497 (PIOI). The single solvent systems evaluated were PG, TC, PGML, IPM, ISIS and CAP. For the binary solvent systems, PG and TC were examined. Ternary solvent systems consisted of: PG, TC and LAB; PG, PGML and LAB; and PG, TC and IPM. The concentration of OPX used was 1% (w/v). Heat-separated human epidermis was used for 24 h permeation experiments performed under finite dose conditions; mass balance studies were also conducted. For the six single solvents examined no permeation was evident. Skin permeation of OPX was observed for binary and ternary solvent systems. The highest permeation for all PG:TC binary solvent system ratios tested was from the PG:TC (75:25) system. For the ternary solvent systems investigated, highest cumulative permeation of OPX was observed for PG:PGML:LAB (60:30:10). Considering all systems, PG:TC (75:25) delivered the greatest amount of OPX through the skin. Although OPX is deposited in the skin following the application of neat solvents, higher skin retention values were generally observed for binary and ternary systems. To our knowledge, this is the first study to examine the permeation behaviour of OPX for a range of single, binary and ternary solvent systems. La perturbation de la barrière protectrice de la couche cornée augmente la vulnérabilité de la peau aux micro‐organismes et facilite des affections telles que les pellicules. Les pellicules sont un trouble du cuir chevelu qui provoque une augmentation de la desquamation de la couche cornée et qui est associé au champignon Malassezia. Par conséquent, de nombreux produits commerciaux antipelliculaires utilisent des principes actifs antifongiques, tels que la piroctone olamine, également appelée Octopirox (OPX). L’OPX est un principe actif utilisé dans un certain nombre de préparations topiques pour la prise en charge des pellicules. La caractérisation des propriétés physicochimiques de l’OPX a été précédemment rapportée. L’objectif de ce travail était d’étudier un éventail de systèmes de solvants pour leurs effets sur l’interaction de l’OPX avec la peau humaine. MÉTHODES: Les solvants utilisés dans cette étude étaient le propylène glycol (PG), l’éther monoéthylique de diéthylèneglycol ou Transcutol® (TC), le monolaurate de propylène glycol (PGML), le myristate d’isopropyle (IPM), le triglycéride caprylique/caprique ou Labrafac™ lipophile WL 1349 (LAB), le caprylate de propylène glycol ou Capryol® 90 (CAP), l’isostéarate d’isostéaryle (ISIS) et Plurol® Oleique CC 497 (PIOI). Les systèmes à solvant unique évalués étaient le PG, le TC, le PGML, l’IPM, l’ISIS et le CAP.

In vivo human studies are considered to be the "gold standard" when investigating (trans)dermal delivery of actives. Previously, we reported the effects of a range of vehicles on the delivery of niacinamide (NIA) using conventional Franz cell studies. In the present work, dermal delivery of NIA was investigated in vivo in human subjects using confocal Raman spectroscopy (CRS) and tape stripping (TS). The vehicles investigated included propylene glycol (PG), Transcutol ® P (TC), binary combinations of PG with oleic acid (OA) or linolenic acid (LA) and a ternary system comprising of TC, caprylic/capric triglyceride (CCT) and dimethyl isosorbide (DMI). For the CRS studies, higher area under curve (AUC) values for NIA were observed for the PG:LA binary system compared with PG, TC and TC:CCT:DMI ( p < 0.05). A very good correlation was found between the in vitro cumulative permeation of NIA and the AUC values from Raman intensity depth profiles, with a Pearson correlation coefficient (R 2 ) of 0.84. In addition, an excellent correlation (R 2 = 0.97) was evident for the signal of the solvent PG and the active. CRS was also shown to discriminate between NIA in solution versus crystalline NIA. The findings confirm that CRS is emerging as a powerful approach for dermatopharmacokinetic studies of both actives and excipients in human.

This study aimed to evaluate the effect of solid lipid and oil structures on the physicochemical properties, kinetic release, photostability, and photoprotection of nanostructured lipid carriers (NLC) containing octyl methoxycinnamate (OMC). OMC was used as a model compound since it is an effective sunscreen agent and is widely used in sunscreen products; however, it is unstable after ultraviolet radiation (UVR) exposure. OMC-loaded NLC were prepared from different solid lipids (cetyl palmitate (CP) or tristearin) and oils (caprylic/capric triglyceride, isopropyl myristate or isononyl isononanoate) at a 4:1 ratio. After production, the particle size (z-ave) and polydispersity index (PDI) of OMC-loaded NLC ranged from 190 to 260 nm and were lower than 0.25, respectively, and the zeta potential (ZP) values were higher than |50 mV|. The Fourier transform infrared (FTIR) spectroscopy results indicated no interaction among the components. Data obtained from differential scanning calorimetry (DSC) and X-ray diffraction showed that the incorporation of oil into solid lipids disturbed the crystallinity of the lipid matrix, depending on the structure of the oil molecule. OMC loaded in tristearin-based NLC (OMC-tristearin-NLC) showed higher release of OMC than OMC loaded in CP-based NLC (OMC-CP-NLC). For photostability properties, OMC-CP-NLC prepared from isononyl isononanoate showed the highest stability owing to the less-ordered structure, providing space for accommodation of OMC, whereas the percentage of OMC remaining in tristearin-based NLC was comparable. Therefore, the degree of protection was dependent on the type of solid lipid and oil. As a result, branched-chain fatty acids provided a higher degree of disturbance than linear-chain fatty acid.

Zinc oxide nanoparticles (ZnO NPs) are a key constituent of many commercial broad-spectrum sunscreens. Studies have shown that these NPs are retained on the superficial layers of the skins' barrier layer, the stratum corneum, and solubilized zinc species from the ZnO NPs have been shown qualitatively to penetrate intact human skin. The cytotoxicity of zinc is concentration- and species-dependent; however, to date, the amount of zinc permeating the skin strata is yet to be determined. Here, we applied commercial ZnO NPs to intact and impaired ex vivo barrier human skin. Artificial human sweat (to provide an electrolyte solution) and caprylic capric triglyceride (CCT; a common sunscreen formulation base) suspensions were applied to encompass potential "in-use" scenarios. A state-of-the-art multimodal approach analyzed zinc permeation. Our data show that elevated zinc concentrations within the skin are dependent on a number of variables, with barrier impairment and time being the most important factors followed by the vehicle, where sweat was more impactful than CCT. When ZnO NPs were applied to impaired barrier skin for 24 h, there was a 60-65-fold increase in zinc in the viable epidermis for both CCT and sweat compared to the control, increasing >100-fold after 48 h. Importantly, we identify that the localized cutaneous zinc concentration increase is not present as the nano ZnO that is used in sunscreens but only after dissolution and permeation as a different solubilized zinc species.

Starch nanocrystals (SNCs) grafted with octenyl succinic anhydride (OSA) were used to stabilize caprylic/capric triglycerides (GTCC)-in-water emulsions. The morphology and viscoelasticity of emulsions were studied in terms of particle loadings and degrees of substitution (DSs). It is found that the emulsifying capacities of SNCs increase with increased DSs. Both the pristine SNC and modified ones can be well used to stabilize emulsions, whereas the emulsification follows different mechanisms. The platelet-like structure of SNCs, together with its improved amphiphilicity after surface treatments, are important to the formation and evolution of droplet clusters. The deformation and relaxation of those clusters result in weak flow overshoots and strong thixotropy in different shear flow fields, which favor storage and applications of GTCC-in-water emulsions as hydrocolloids. The mechanisms were then discussed in terms of rigidity of SNC and relaxations of clusters. This work proposes a promising application of SNC in food and cosmetic industries.

When it comes to Pickering emulsions, the first question that arises is the ability of a particle to position itself at the oil/water interface and then ensure stabilization of the emulsion formed. However, when we try to transpose this type of emulsion to industrial requirements, for example, another question arises: can the sole presence of particles enable us to obtain stable, homogeneous and fully emulsified emulsions? We have been able to prove, for the first time, that pristine bentonite particles, which have not undergone any modification to their surface chemistry, are capable of stabilizing emulsions for at least two years. To this end, we have shown that the emulsification process must be accompanied by very high shear. In fact, only a process in which the particles were subjected to high-energy ultrasound (25-30 kJ) showed this high stabilization capacity. Spectroscopy, surface free energy measurement, and microscopic characterizations confirmed that at this stage these pristine bentonite particles remained unchanged, except for their morphology. A very simple formula containing water, 4 % particles, 20 % Caprylic/Capric Triglyceride and 1 % preservative has demonstrated its ability to form a fully emulsified, homogeneous and stable Pickering emulsion, Rheological and microscopic measurements of the formulated emulsion clearly show that part of the particles are positioned at the interface as expected and moreover that it is through the organization of a 3D network of particles present in excess in the continuous phase that this Pickering emulsion achieves both homogeneity and stability. Our methodology provides a robust approach for explaining the relevant parameters for obtaining a fully emulsified and stable emulsion over time, using pristine, non-modified, bentonite particles for topical applications.

As a well-known aromatic herb rich in various bioactive molecules, the extract of Crithmum maritimum is widely used in cosmetics. However, the extraction process for Crithmum maritimum is far from perfect. Moreover, the water- and oil-soluble components are too complex to be compatible with each other. Thus, the traditional water- or oil-based extracts of Crithmum maritimum encompass only water- or oil-soluble components, respectively. The effective components being incomplete results in significantly reduced effects. Therefore, obtaining a full-component extract of Crithmum maritimum is imperative to ensure its full functionality. Herein, a full-component extract of Crithmum maritimum based on miscibility between polyol and oil was developed by extracting water-soluble active substances with a ternary solvent, followed by mixing them with oil extracts of Crithmum maritimum . In ternary solvents, most water-soluble compounds of Crithmum maritimum can be extracted by ethanol. During evaporation, the water-soluble components are transferred and dissolved in hexanediol from the solvent. Thus, by blending hexanediol with caprylic/capric triglyceride (GTCC), we successfully created a potent full-component extract of Crithmum maritimum . Through the study of the barrier-weakening 3D full-skin model, it was found that the full-component extract of Crithmum maritimum , rich in chlorogenic acid, could significantly promote the epidermal regeneration of UV-induced skin damage compared to the oil-based extract components.

Natural moisturizing factor (NMF) includes several compounds in the stratum corneum (SC), among them, urocanic acid (UCA). Ultraviolet (UV) exposure turns the trans -UCA of the SC into its cis isomer. We investigated the impact of a topical emollient emulsion treatment on the UCA isomers of the SC exposed to artificial UV stress. Aliquots of emollient emulsion were applied in healthy subjects for 2 h on delimited areas of the volar forearm, then, the SC was removed by tape stripping. Tapes were irradiated in a solar simulator chamber and a high performance liquid chromatograph was used to quantify UCA isomers from stripped SC extract. The amount of both UCA isomers were almost twice higher in the SC treated with the emollient emulsion. We also observed that the UV irradiation elevated the amount of the cis / trans UCA ratio on the SC (non-treated and treated), suggesting that the emollient sample was not able to avoid the UCA isomerization. The in vivo tests corroborated with the UCA data obtained ex vivo, since we found an increase in the superficial skin hydration with respective reduction of the TEWL, probably occurring by the occlusion performed by the emollient emulsion containing 15.0% w / w of caprylic/capric triglyceride.

The purpose of this study is to produce nanostructured lipid carrier (NLC) that can solubilize poorly water-soluble velutin and verify an improved tyrosinase synthesis inhibition. A solubility test for velutin was conducted. Cetyl palmitate and caprylic/capric triglyceride were selected as solubilizer. The lipid matrix was produced using the ultrasound dispersion method. The morphology and size distribution of the produced NLC was analyzed through scanning electron microscopy (SEM) and dynamic light scattering (DLS), and the release and tyrosinase inhibition of velutin was evaluated through the Franz diffusion cell method and tyrosinase inhibition assay. Lipid matrix nanoparticles showed an average size of approximately 250 nm and polydispersity of 0.2, and it was confirmed that the velutin incorporated within nanoparticles sustained release at a constant rate over 36 hours. Due to extremely low aqueous solubility, the tyrosinase synthesis inhibition of velutin suspension was 0%, and the value of velutin incorporated within the NLC formulation was greatly improved 56.5% (40 μg/mL). As a result, it was verified that lipid-based NLC nanoparticles are an efficient formulation for the topical delivery of poorly water-soluble flavonoids such as velutin.