Towards satisfying performance of an O/W cosmetic emulsion: screening of reformulation factors on textural and rheological properties using general experimental design.

OBJECTIVE: Consumers' demand for improved products' performance, alongside with the obligation of meeting the safety and efficacy goals, presents a key reason for the reformulation, as well as a challenging task for formulators. Any change of the formulation, whether it is wanted - in order to innovate the product (new actives and raw materials) or necessary - due to, for example legislative changes (restriction of ingredients), ingredients market unavailability, new manufacturing equipment, may have a number of consequences, desired or otherwise. The aim of the study was to evaluate the influence of multiple factors - variations of the composition, manufacturing conditions and their interactions, on emulsion textural and rheological characteristics, applying the general experimental factorial design and, subsequently, to establish the approach that could replace, to some extent, certain expensive and time-consuming tests (e.g. certain sensory analysis), often required, partly or completely, after the reformulation. METHODS: An experimental design strategy was utilized to reveal the influence of reformulation factors (addition of new actives, preparation method change) on textural and rheological properties of cosmetic emulsions, especially those linked to certain sensorial attributes, and droplet size. RESULTS: The general experimental factorial design revealed a significant direct effect of each factor, as well as their interaction effects, on certain characteristics of the system and provided some valuable information necessary for fine-tuning reformulation conditions. Upon addition of STEM-liposomes, consistency, index of viscosity, firmness and cohesiveness were decreased, as along with certain rheology parameters (elastic and viscous modulus), whereas maximal and minimal apparent viscosities and droplet size were increased. The presence of an emollient (squalene) affected all the investigated parameters in a concentration-dependent manner. Modification of the preparation method (using Ultra Turrax instead of a propeller stirrer) produced emulsions with higher firmness and maximal apparent viscosity, but led to a decrease in minimal apparent viscosity, hysteresis loop area, all monitored parameters of oscillatory rheology and droplet size. CONCLUSION: The study showed that the established approach which combines a general experimental design and instrumental, rheological and textural measurements could be appropriate, more objective, repeatable and time and money-saving step towards developing cosmetic emulsions with satisfying, improved or unchanged, consumer-acceptable performance during the reformulation.

Polyhydroxy surfactants for the formulation of lipid nanoparticles (SLN and NLC): effects on size, physical stability and particle matrix structure.

The two polyhydroxy surfactants polyglycerol 6-distearate (Plurol(®)Stearique WL1009 - (PS)) and caprylyl/capryl glucoside (Plantacare(®) 810 - (PL)) are a class of PEG-free stabilizers, made from renewable resources. They were investigated for stabilization of aqueous solid lipid nanoparticle (SLN) and nanostructured lipid carrier (NLC) dispersions. Production was performed by high pressure homogenization, analysis by photon correlation spectroscopy (PCS), laser diffraction (LD), zeta potential measurements and differential scanning calorimetry (DSC). Particles were made from Cutina CP as solid lipid only (SLN) and its blends with Miglyol 812 (NLC, the blends containing increasing amounts of oil from 20% to 60%). The obtained particle sizes were identical for both surfactants, about 200 nm with polydispersity indices below 0.20 (PCS), and unimodal size distribution (LD). All dispersions with both surfactants were physically stable for 3 months at room temperature, but Plantacare (PL) showing a superior stability. The melting behaviour and crystallinity of bulk lipids/lipid blends were compared to the nanoparticles. Both were lower for the nanoparticles. The crystallinity of dispersions stabilized with PS was higher, the zeta potential decreased with storage time associated with this higher crystallinity, and leading to a few, but negligible larger particles. The lower crystallinity particles stabilized with PL remained unchanged in zeta potential (about -50 mV) and in size. These data show that surfactants have a distinct influence on the particle matrix structure (and related stability and drug loading), to which too little attention was given by now. Despite being from the same surfactant class, the differences on the structure are pronounced. They are attributed to the hydrophobic-lipophilic tail structure with one-point anchoring in the interface (PL), and the loop conformation of PS with two hydrophobic anchor points, i.e. their molecular structure and its interaction with the matrix surface and matrix bulk. Analysis of the effects of the surfactants on the particle matrix structure could potentially be used to further optimization of stability, drug loading and may be drug release.

An alkylpolyglucoside surfactant as a prospective pharmaceutical excipient for topical formulations: the influence of oil polarity on the colloidal structure and hydrocortisone in vitro/in vivo permeation.

There is a growing need for research into new skin- and environment-friendly surfactants. This paper focuses on a natural surfactant of an alkylpolyglucoside type, which can form both thermotropic and lyotropic liquid-crystalline phases. The aim of this study was to relate some physicochemical properties (characterised by polarisation and transmission electron microscopy, thermal analysis and rheology) of the three formulations based on cetearyl glucoside and cetearyl alcohol, to the results of in vitro and in vivo bioavailability of hydrocortisone (HC). The three formulations contained oils of different polarity (medium chain triglycerides: MG, isopropyl myristate: IPM and light liquid paraffin: LP), respectively. In vitro permeation was followed through the artificial skin constructs (ASC), while the parameters measured in vivo were erythema index: EI (using instrumental human skin blanching assay), transepidermal water loss (TEWL) and stratum corneum hydration (SCH). The vehicles based on cetearyl glucoside and cetearyl alcohol showed a complex colloidal structure of lamellar liquid-crystalline and lamellar gel-crystalline type, depending on oil polarity. Rheological profile of the vehicle was directly related to the in vitro profile of the HC permeation. In vivo results suggested that the vehicle with MG retarded the HC permeation, whereas less polar IPM and non-polar LP enhanced it. It is suggested that the enhancement is achieved either by a direct interaction with lipid lamellae of the SC or indirectly by improving skin hydration. There were no adverse effects during in vivo study, which indicates a good safety profile of this alkylpolyglucoside surfactant.

The characterization of the semi-solid W/O/W emulsions with low concentrations of the primary polymeric emulsifier.

Semi-solid multiple W/O/W emulsions with low concentrations (0.8, 1.6 and 2.4% w/w) of lipophilic polymeric primary emulsifier PEG-30-dipolyhydroxystearate (PDHS) have been formulated. Both emulsions, primary and multiple, were prepared with high content of inner phase (Phi1 = Phi2 = 0.8). All the formulations differ only in the lipophilic emulsifier concentration. Evaluating several parameters such as macroscopic and microscopic aspect, droplet size, accelerated stability under centrifugation and flow and oscillatory rheological behaviour, assessed the multiple systems. It is possible to formulate the semi-solid W/O/W multiple emulsions with low concentrations of PDHS as the primary emulsifier. It appeared that the highest long-term stable multiple emulsion with the lowest droplet size, the highest apparent viscosity and highest elastic characteristic, was the sample with the highest concentration (2.4% w/w) of the primary emulsifier.

Vehicle-controlled effect of urea on normal and SLS-irritated skin.

It is known that, depending on the concentration, treatment with urea could improve skin barrier function, despite its penetration-enhancing properties. This controversial skin effect of urea has been explored systematically in this study in terms of the effect of vehicle on the performance of urea. In the first part, a series of four semi-solid emulsions with 5% (w/w) urea, varying in the type of emulsion, nature of emulsifier and polarity of oil ingredients, have been evaluated with regard to their skin hydrating and transepidermal water loss (TEWL)-modifying properties. Placebo samples were tested alongside the urea-containing ones. Two best performing moisturisers from the above were chosen for the second part of the study, in which sodium lauryl sulphate (SLS)-irritated skin was treated with both placebo and urea-containing samples. In addition to TEWL and skin hydration level, the erythema index (EI) was measured before, during and after the treatment. The results have shown that barrier-improving and hydrating abilities of urea are bi-directional and dependent on both the type of vehicle used for its delivery and the state of skin.

Influence of liposomes on the stability of vitamin a incorporated in polyacrylate hydrogel.

Lecithin has an antioxidative potential that depends directly on the content of phospholipids. Purified lecithin with a higher phospholipid content exerts better antioxidative properties. Furthermore, due to its specific physico-chemical properties, amphiphility in particular, the phospholipid the largest portion of the lecithin lipids, forms enclosed membrane systems (liposomes) in the presence of water. Liposomes encapsulate hydro and liposoluble, pharmacologically and cosmetically active components. The relatively poor stability of vitamin A considerably limits its use in topical preparations. Protection against an oxidation process is the main reason for vitamin A encapsulation in the liposomes made from the purified phospholipid fraction (90% phosphatidyl choline). It increases the vitamin A-palmitate stability against the oxidation process caused by UV radiation. Lecithin used for preparing the liposomes increases vitamin A stability during UV radiation in pure liposome dispersion or liposomes with vitamin A incorporated in polyacrylate gel as a vehicle.

Assessment of Efficiency of Repellent Formulations with N,N-diethyl-m-toluamide in Laboratory Conditions.

The affinity of N,N-diethyl-m-toluamide) (DEET) for various polymers that are potential inert carriers (PEG, PVP, NaCMC, PAA) was studied. Mixtures of DEET and the polymers were prepared and analysed for DEET vapour release using head space analysis. Polyvinylpyrrolidone (PVP) showed the highest affinity for DEET. Several insect repellent formulations in the form of a hydrogel, an o/w cream and a stick were prepared with 5% w/w DEET and either 1% w/w or no PVP. The release of DEET from the formulations was investigated by Head Space gas-mass spectrometry at 32 degrees C. The degree of absorption of DEET through the skin was evaluated by applying these topical preparations to shaved rabbit skin and measuring DEET content in the blood samples by gas-mass spectrometry at various time intervals after application. Based on these results the pharmacokinetic parameters were determined. The minimum penetration of DEET through rabbit skin was obtained with a hydrogel containing PVP as a carrier. The biological efficiency of repellent formulations containing 5% DEET (w/w) was evaluated for repellency using the mosquito Aedes aegypti. The results demonstrated that the hydrogel formulation based on polyacrylic acid containing 5% DEET (w/w) supplemented with 1% PVP (w/w), could serve as a suitable vehicle for repellent preparations containing DEET.

The Influence of Processing Variables on Performance of O/W Emulsion Gels Based on Polymeric Emulsifier (Pemulen (R)TR-2NF).

Pemulens(R) (BF Goodrich) are hydrophobically-modified copolymers of acrylic acid (Acrylates/C10-C30 alkyl acrylates) that could act both as primary emulsifiers for o/w emulsions and viscosity enhancing agents. The aim of this study was to assess the influence of different processing conditions (mixing equipment, speed and time of agitation) on the aesthetic characteristics, viscosity and physical stability of o/w emulsion gels based on the polymeric emulsifier (Pemulen TR-2 NF). This objective was achieved by applying a two-factor three-level experimental design at two sets: using a laboratory mixer and a disperser. Independent variables were mixing speed and time and dependant variables i.e. responses, were millimetres of oil phase separated after centrifugation at 3500 rpm in a laboratory centrifuge, and viscosity at shear rate 180 l/s. The responses were fitted into a second order model by means of a multiple regression analysis. For the samples prepared on the laboratory mixer it was shown that mixing time and speed produce a statistically important influence on viscosity, but not on physical stability: with increasing mixing speed and time the viscosity linearly increases. If we assume that greater energy input obtained by increasing the mixing speed and time produces a decrease in drop size and polydispersity and better developed gel network, then the optimal processing conditions will be at the point where maximal viscosity is attained. This result was in accordance with the centrifugation test - the best stability appeared when maximal mixing speed and time were applied, although this effect appeared not to be statistically significant. For samples prepared using dispersers no statistically important influence of processing variables on viscosity and physical stability was found. Additionally, emulsion samples prepared using the laboratory mixer appeared homogenous, while in samples prepared using the disperser, undispersed polymer lumps appeared. Based on physical characteristics of the emulsions, it could be concluded that the disperser is an inappropriate tool for processing the emulsions based on Pemulen polymers.

An investigation into the use of thermorheology and texture analysis in the evaluation of W/O creams stabilized with a silicone emulsifier.

The aim of the study was to evaluate a range of W/O semisolid emulsion systems (creams) containing white soft paraffin (petrolatum) and a new type of nonionic lipophilic silicone emulsifier (Abil EM 90) using a novel combination of rheological tests. Emulsifier concentrations from 1.5% to 3.0% w/w were used with two manufacturing procedures, cold (25 degrees C) and warm (70 degrees C) emulsification, to determine whether and to what extent these variables alter the structure and consistency of the creams. The techniques comprised linear (continuous flow) and dynamic (oscillatory) rheometry at 25 degrees C, thermal flow experiments (from 10 degrees to 90 degrees C and back to 10 degrees C), and penetrometry studies. The differences in emulsifier concentration produced effects on the rheological properties of the W/ O creams, although the manufacturing process was much more influential. Cold emulsification led to creams with higher viscosity, lower thixotropy, and better elastic properties. The results of penetration tests on creams correlated with those of the rheological studies. The flow properties of white soft paraffin at 25 degrees C were comparable with the creams obtained by cold emulsification, while the elasticity was considerably lower. Thermorheological studies showed evidence for transitional behavior for white soft paraffin on heating, but not for the creams. White soft paraffin showed a higher viscosity (and resistance to the penetrating force) when melted at 70 degrees C and left to solidify at room temperature, compared to the "unmelted" sample. This was the opposite trend to that found with warm and cold emulsified creams. The input of heat during the emulsification process showed a strong effect on the structure and consistency of the W/O creams containing petrolatum and silicone emulsifier, resulting in a less viscous product. The use of the aforementioned techniques represents a useful and novel approach to the evaluation of cream consistency.

In vitro release of calcium and hydroxyl ions from two types of calcium hydroxide preparation.

Non-setting and setting pastes are the most common forms of calcium hydroxide, used in endodontics. The aim of this study was to investigate the differences in the availability of calcium and hydroxyl ions from some commercial preparations of both types. In vitro released calcium and hydroxyl ions were determined by a potentiometric method, after diffusion through sintered glass. The non-setting pastes evaluated were Calcipulpe, Calxyl Red, Calxyl Blue and Cinacal; while setting base materials were represented by Dycal, Nu-Cap and Reolit. The data obtained showed significantly higher availability of calcium and hydroxyl ions from non-setting pastes, compared with 'alkaline cements' (P < 0.05). Great variations in the amount of released ions were also found among samples of the same material.

[New medicine forms of controlled release of fluorides into enamel]. / Novi lekoviti oblici za kontrolisano oslobadanje fluorida na povrsinu gledi.

The article deals with the description of the therapeutic system for the local application on fluorides, principles of its functioning, advantage upon classical dosages, as well as a short survey of previous attempts of its formulation.