Characterization and evaluation of free and nanostructured ursolic acid incorporated in cosmetic formulation using thermal analysis

The ursolic acid (UA) increases the skin’s barrier function and acts in epidermal differentiation of keratinocytes in the epidermis, promoting cell renewal. Besides the mentioned properties UA also has antioxidant, antimicrobial, and anti-irritant functions to cosmetic formulations. Thus, it is necessary formulation studies to insure the development of quality cosmetic products containing this active, increasing its antioxidant potential within nanoparticles. This study aims to characterize and evaluate the thermal behavior of UA in free and nanostructured forms, and both incorporated into a cosmetic base formulation, using thermogravimetry and differential scanning calorimetry. Through the study were observed that free UA, in the embedded nanoparticles and in base formulation exhibited different behavior in similar thermal profile and relative to the presence of UA. The UA remained stable to a temperature of 250 °C and the technique has been shown to be effective for characterizing UA, evaluate water content, and stability of the formulation base.     

Development and evaluation of microencapsulated sunscreen

The aim of the present study was to carry out stability tests and in vitro sun protection factor (SPF) evaluations of formulations containing free or microencapsulated chemical sun filters to improve their use. To this end, three formulations were developed and subjected to stability studies. The most stable formulation was chosen as a vehicle for free and microencapsulated chemical sun filters, and subjected to further stability studies and in vitro SPF assays. The SPF values were approximately 12 and 11 for formulations containing free and encapsulated sun filters, respectively, and both types were stable under stress. Chemical sun filters can be microencapsulated, which may aid in generating innovative sunscreen formulations.     

A HPLC method to evaluate the influence of photostabilizers on cosmetic formulations containing UV-filters and vitamins A and E

This paper reports a simple and reliable HPLC method to evaluate the influence of two currently available photostabilizers on cosmetic formulations containing combined UV-filters and vitamins A and E. Vitamins and UV-filters, widely encountered in products of daily use have to be routinely evaluated since photoinstability can lead to reductions in their efficacy and safety. UV-irradiated formulation samples were submitted to a procedure that included a reliable, precise and specific HPLC method employing a C18 column and detection at 325 and 235 nm. Methanol, isopropanol and water were the mobile phases in gradient elution. The method precision was between 0.28 and 5.07. The photostabilizers studied [diethylhexyl 2,6-naphthalate (DEHN) and benzotriazolyl dodecyl p-cresol (BTDC)], influenced the stability of octyl methoxycinnamate (OMC) associated with vitamins A and E. BTDC was considered the best photostabilizer to vitamins and OMC when the UV-filters were combined with both vitamins A and E.     

In vitro antioxidant and in vivo photoprotective effects of an association of bioflavonoids with liposoluble vitamins

A new tendency in cosmetic formulations is the association of botanical extracts and vitamins to improve skin conditions by synergic effects. The objective of this study was to determine the antioxidant activity of associated bioflavonoids, retinyl palmitate (RP), tocopheryl acetate (TA) and ascorbyl tetraisopalmitate (ATIP), as well as their photoprotective effects in preventing increased erythema, transepidermal water loss (TEWL) and sunburn cell formation in hairless mouse skin. The antioxidant activity of solutions containing the association or each substance separately was evaluated in vitro by a chemiluminescence assay. The photoprotective effect was evaluated by means of in vivo tests. Dorsal skin of hairless mice was treated daily by topical applications for 5 days with formulations containing or not containing (vehicle) the flavonoid-vitamins association (5%). The skin was irradiated (UVA/B) 15 minutes after the last application. The results showed that bioflavonoids had in vitro antioxidant properties and also that when they were associated with vitamins their antioxidant activity was more pronounced. On the other hand, erythema and UV damage to the permeability barrier function (TEWL) was not significantly reduced by previous treatment with the flavonoid-vitamin-association formulations, when compared to the irradiated vehicle-treated area. However, the treatment protected the skin from UV damage because it reduced the number of sunburn cells, when compared to the vehicle-treated area. Finally, the association of vitamins and bioflavonoids added to a dermocosmetic formulation showed a relevant biological activity in terms of photoprotection, because the association of bioflavonoids and vitamins acted by different mechanisms, such as antioxidation and absorption of UV radiation, which suggests its use in antiaging and photoprotective products.     

An overview on chemical derivatization and stability aspects of selected avermectin derivatives

Naturally occurring avermectins (AVMs) and its derivatives are potent endectocide compounds, well-known for their novel mode of action against a broad range of nematode and anthropod animal parasites. In this review, chemical and pharmaceutical aspects of AVM derivatives are described including stability, synthetic and purification processes, impurities and degradation pathways, and subsequent suggestions are made to improve the chemical stability. It has been found out that unique structure of AVM molecules and presence of labile groups facilitated the derivatization of AVM into various compounds showing strong anthelmintic activity. However, the same unique structure is also responsible for labile nature related to sensitive stability profile of molecules. AVMs are found to be unstable in acidic and alkaline conditions. In addition, these compounds are sensitive to strong light, and subsequently presence of photo-isomer in animals treated topically with AVM product is well known. The pharmacoepial recommendations for addition of antioxidant into drug substance, as well as its products, arises from the fact that AVM are very sensitive to oxidation. Formations of solvates, salts, epoxides, reduction of double bonds and developing liquid formulation around pH 6.2, were some chemical approaches used to retard the degradation in AVM. This coherent review will contribute towards the better understanding of the correlation of chemical processes, stability profile and biological activity; therefore, it will help to design the shelf-life stable formulations containing AVMs.     

Influence of the photostabilizer in the photoprotective effects of a formulation containing UV-filters and vitamin A

Vitamin A palmitate has been used in cosmetics; however, studies report that this substance shows photoreactivity that can lead to loss of safety and efficacy. On the other hand, photostabilizers have been used to increase sunscreen photostability and consequently their safety and effectiveness. Thus, this study aimed to evaluate the influence of photostabilizers on the photoprotective effects of a cosmetic formulation containing UV-filters and vitamin A palmitate. The formulation containing UV-filters was supplemented with vitamin A palmitate and the photostabilizers diethylhexyl 2,6-naphthalate (DEHN), bumetrizole and benzotriazolyl dodecyl p-cresol (BTDC). Hairless mice were treated daily by topical applications and irradiated (UVA/B). Erythema index, transepidermal water loss, histological/histometric analysis and number of sunburn cells (SBC) were evaluated. The results showed that all formulations protected from UV-induced enhancement of erythema and SBC but there was no difference among them. The formulation with no stabilizers reduced viable epidermis thickness due to atrophy induced by UV radiation. Thus, it can be concluded that the presence of photostabilizers influenced the effects of formulations containing UV-filters and vitamin A palmitate, which could be seen by histological and histometric analysis. Furthermore, the formulations containing the stabilizers DEHN and BTDC showed better protective effects on hairless mice skin.     

Evaluation of nanoherbal gel for anti-warts activity

In the present experimental investigation a novel nanoherbal gel containing iron nanoparticles and extract from Cuscuta reflexa was used as a drug. Synthesized nanoherbal increased the drug solubility and penetration in the skin and is useful as a novel delivery system for better anti-warts activity. The experimental work includes preformulation studies of drug (Cuscuta reflexa) which include organoleptic properties, identification and solubility studies. Spectroscopy characterization was performed for identification of drug. The iron nanoparticles were evaluated for their characteristic such as appearance, viscosity and odor. Various formulations F1–F5 was prepared using different formulation variables based on experiment design. The result showed that the formulation F-5 provide the better release using 5.5 pH acetate buffer and at 37 °C temperature for anti-warts activity. The maximum drug release through synthesized nanoherbal gel was found to be 91.3%. Nanoherbal formulation was evaluated for physical appearance, pH, consistency, spreadibility and drug content. Stability study of formulation F5 was carried out for a period of 3 months to determine the percentage release and the results revealed that the formulation is stable under varied humidity and temperature condition and there was no major change in the amount of drug release during the storage condition, which reflected the stability of F5 formulation.     

Photoprotective nanoemulsions containing microbial carotenoids and buriti oil: Efficacy and safety study

Photoprotective nanoemulsions are able to attenuate skin damage from overexposure to the sun, thus avoiding the immediate effects caused by ultraviolet radiation. The global cosmetics market understands that there is a demand and greater acceptance by consumers for formulations containing natural products compatible with the skin. Consequently, there is an increasingly need to develop such products that are safe and effective. Furthermore, there is a growing interest in nanoemulsions (NE) in the pharmaceutical industry, due the versatility of incorporating lipophilic substances into cosmetic formulations. In the present work, oil-in-water photoprotective nanoemulsions containing microbial carotenoids, buriti oil and chemical filters were developed and characterized. The essential physical properties of the droplets, the transmission electronic microscopy (TEM), the sun protection factor (SPF) as well as the stability of the formulations were determined. In vitro phototoxicity was evaluated using Balb 3 T3 with relative cell viability estimated by Neutral Red Uptake, with the Photo Irritation Factor (PIF) and the Medium Photo Effect Factor (MPF) as the measurement parameters. Nanoemulsion 3 (NE3) showed spherical morphology with an average droplet size of 142.11 ± 0.92 nm and polydispersity index (PDI) of 0.198 ± 0.017. This nanoemulsion containing microbial carotenoids and buriti oil exhibited a SPF of 36 ± 1.5. Neutral Red Uptake revealed that the cells kept their viability even after irradiation and those nanoemulsions containing the microbial carotenoids and buriti oil were not phototoxic. The addition of microbial carotenoids and buriti oil in nanoemulsions was positive in increasing the mean SPF values compared to the control formulation.     

Phenylglycine derivatives as coinitiators for the radical photopolymerization of acidic aqueous formulations

Aromatic amines are known to give very poor performance as coinitiators for camphorquinone in the photopolymerization of acidic aqueous formulations. Differential scanning photocalorimetry investigations using N‐phenylglycine (NPG) as an alternative coinitiator proved the suitability of this derivative. Furthermore, it was demonstrated that the generally poor photoreactivity had to be assigned to the presence of water and not to the acidity of the formulation. The poor storage stability of NPG‐containing formulations was significantly improved by derivatives containing electron‐withdrawing substituents in the para position of the aromatic moiety, and the photoreactivity was kept at a very high level. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 115–125, 2006     

Stopped-flow Fourier-transform infra-red spectrometric speciation of glycolic and lactic acids in cosmetic formulations

The dermatological activity of cosmetic formulations containing alpha-hydroxyacids depends on their different chemical forms, and it is therefore useful to determine these species in the finished products. In the present report a new procedure for studying the protonation equilibria of glycolic and lactic acids by stopped-flow Fourier-transform infra-red (FTIR) spectrometry is described. The procedure was validated for use in the speciation of glycolic and lactic acids in cosmetic formulations, with preferential attention given to glycolic acid, which is the most widely used. Species of these alpha-hydroxyacids can be approximately determined at different pHs and the total content of each alpha-hydroxyacid can be accurately determined (according to the Student t-test at 5% significance level). The recovery of the total content of glycolic acid from commercial cosmetic formulations was 101+/-4%. The RSD of the determinations of the total content and those of the species was of the order of 2-7%.     

Influence of particle design on oral absorption of poorly water-soluble drug in a silica particle-supercritical fluid system

The physicochemical characteristics and oral absorption of a poorly water-soluble drug, K-832, adsorbed onto porous silica (Sylysia 350), were compared with those of K-832 adsorbed onto non-porous silica (Aerosil 200). K-832 and silica were treated with supercritical CO(2) (scCO(2)) to produce K-832-Sylysia 350 and K-832-Aerosil 200 formulations. Scanning electron microscopy, polarizing microscopy, powder X-ray diffraction, and differential scanning calorimetry results suggested that K-832 mainly existed in an amorphous state in both formulations. The specific surface area of both formulations was much larger than that of pure K-832 crystals. The dissolution rate of K-832 from both formulations was considerably greater than that from corresponding physical mixtures due to rapid wetting of the hydrophilic carrier surfaces and amorphous state, the dissolution from the K-832-Sylysia 350 formulation being the fastest. In vivo absorption tests on the two formulations indicated no significant differences in their peak concentration (C(max)) and the area under their plasma concentration-time curve (AUC), while the concentrations of K-832 in the K-832-Sylysia 350 formulation were significantly higher than those in the K-832-Aerosil 200 formulation 1 h and 1.5 h after administration of these formulations (p<0.05). This could be attributed to the different dispersion states of K-832 in the formulations due to their different three-dimensional structures (porous and non-porous). In physical stability tests, the amorphous drugs in both formulations were stable at room temperature for at least 14 months. Thus, the absorption of poorly water-soluble drugs could be greatly improved by adsorption onto porous silica using scCO(2).     

Efficacy of cosmetic formulations containing dispersion of liposome with magnesium ascorbyl phosphate, alpha-lipoic acid and kinetin

The present study aimed to evaluate the photoprotective effects of cosmetic formulations containing a dispersion of liposome with magnesium ascorbyl phosphate (MAP), alpha-lipoic acid (ALA) and kinetin, as well as their effects on the hydration and viscoelastic skin properties. The photoprotection was determined in vitro (antioxidant activity) and in vivo on UV-irradiated hairless mouse skin. The hydration effects were performed with the application of the formulations under study on the forearm of human volunteers and skin conditions were analyzed before and after a single application and daily applications during 4 weeks in terms of transepidermal water loss (TEWL), skin moisture and viscoelastic properties. The raw material under study possessed free-radical scavenging activity and the formulation with it protected hairless mouse skin barrier function against UV damage. After 4 weeks of application on human skin, the formulation under study enhanced stratum corneum skin moisture and also showed hydration effects in deeper layers of the skin. Thus, it can be concluded that the cosmetic formulation containing a dispersion of liposome with MAP, ALA and kinetin under study showed photoprotective effects in skin barrier function as well as pronounced hydration effects on human skin, which suggests that this dispersion has potential antiaging effects.     

Formulation studies on a topical gel of tretinoin�Cdimethyl-beta-cyclodextrin complex

The aim of this work was to develop and characterize a 0.05% tretinoin hydrogel formulations in which tretinoin is free or complexed with dimethyl-beta-cyclodextrin in order to compare the main advantages of its complexation. Theoretically, the complexation will mainly allow to: overcome drug low solubility in water and low stability; enhance the drug release by promoting skin absorption and alleviate of drug inducing local irritation. The hydrogels prepared were both microbiological and physically stable during 30 days. However, the chemical stability was less encouraging. The complexed tretinoin gel had also a higher releasing profile than the free tretinoin gel. This study has demonstrated that it is possible to obtain a microbiological and physically stable gel formulation with good releasing profile.     

Liquid crystalline formulations containing modified surface TiO2 nanoparticles obtained by sol–gel process

Titanium dioxide (TiO₂) is an inorganic compound used as sunscreen in cosmetic/pharmaceutical formulations as a way to prevent the skin cancer. In this work we have used surface modified titania nanoparticles obtained by thermo-reversible sol?Cgel transition showing transparency in the range of temperature typical for sunscreen use (between 20 and 45?°C). The goal of this work was to develop and characterize liquid crystalline cosmetic formulations containing surface modified titania nanoparticles. We have analyzed the citotoxicity of the nanoparticles, their zeta potential and the liquid crystalline phase behavior of the formulations. The violet crystal assay has shown no citotoxicity associated to the presence of surface modified groups on the two cell lines tested, human keratinocytes and fibroblasts, presenting more than 70% of cell viability for all analyzed nanoparticles. The zeta potential measurements revealed a negative charged surface for TiO₂ nanoparticles at pH values in the range of 6.5?C7.0, preventing the aggregation and maintaining the final transparency of the liquid crystalline sunscreen formulations. The polarized light microscopy, associated to SAXS, have shown the presence of liquid crystalline phases both with and without TiO₂ nanoparticles. The charged surface of TiO₂ nanoparticles maintains the stability of the formulations and the liquid crystalline structure. This renders this system a good candidate for being used simultaneously as sunscreen and as controlled release system of anti cancer drugs.     

An improved method for the preparations of nanostructured lipid carriers containing heat-sensitive bioactives

Heat-sensitive bioactive compounds such as β-carotene and tocols, are widely used in the pharmaceutical and cosmetic fields. Their chemical stability in delivery systems is one of the major concerns in the production of nanostructured lipid carriers (NLCs). A previously established high-temperature high-pressure homogenisation technique involved in the preparation of NLCs can cause degradation of heat-sensitive compounds. Therefore, a novel preparation process needs to be developed to minimise the degradation of heat-sensitive active compounds during the preparation of NLCs. In this work, modified methods A and B were designed to minimise the degradation of β-carotene and tocols during the production of NLCs. These methods improved the chemical stability of heat-sensitive bioactive compounds (β-carotene and tocols) significantly compared to the previously established method. The physical stability of the formulation was maintained throughout study duration.     

Rapid, practical and predictive excipient compatibility screening using isothermal microcalorimetry

Conditions for conducting excipient compatibility studies via isothermal microcalorimetry were explored using model reactions. The resulting recommended procedure for rapid and practical screening consisted of using binary mixtures (100 mg of each component), the addition of 20% (w/w) water, and monitoring the mixture at 50°C for 3 days using an isothermal microcalorimeter. The correlation between calorimetric excipient compatibility results and formulation stability was investigated for two developmental drugs. A comparison of calorimetric results to actual formulation stability suggested that it was possible to predict relative stability within functional classes. However, caution should be exercised in such predictions, because apparent reaction enthalpies were found to vary three-fold among excipients in the same functional class. Based on these observations, a two-step procedure is suggested for efficient development of stable formulations. First, excipient compatibility screening should be conducted using a rapid calorimetric technique. The calorimetric results are then used to evaluate relative risk of incompatibility for each excipient within a particular functional class. The calorimetric data and the functional requirements of the dosage form are then integrated in developing a limited number of model formulations that are likely to succeed from both a performance and a stability perspective. The second step of the process is to conduct traditional HPLC-based accelerated stability studies on the limited number of model formulations.     

Colon targeted delivery systems of metronidazole based on osmotic technology: development and evaluation

Colon targeted delivery systems of metronidazole (MTZ) based on osmotic technology were developed. The developed systems consisted of osmotic core (drug, osmotic agent and wicking agent), coated with semipermeable membrane (SPM) containing guar gum as pore former, coated core were then further coated with enteric coating to protect the system from acidic environment of stomach. The effect of various formulation variables namely the level of wicking agent (sodium lauryl sulphate), osmotic agent in the osmotic core, the level of pore former (guar gum) in SPM, and the thickness of SPM, were studied on physical parameters and drug release characteristics of developed formulations. MTZ release was inversely proportional to SPM thickness, but directly related to the level of pore former, wicking agent and osmotic agent. On the other hand burst strength of the exhausted shells was decreased with the increase in level of pore former in the membrane but increased with the increase in the thickness of SPM. The drug release from the developed formulations was independent of pH, and agitation intensity, but dependent on the osmotic pressure of the release media. The thickness of enteric coating could prevent formation of delivery pores before contact with simulated colonic fluid, but had no effect on drug release. Result of SEM studies showed the formation of in-situ delivery pores in the membrane from where the drug release occurred, and the number of pores formed were directly related to the initial level of pore former (guar gum) in SPM. The manufacturing procedure was found to be reproducible and formulations were found to be stable during 3 months of accelerated stability studies.     

Analysis of semipermanent hair dyes by HPLC with on-line post-column photochemical derivatisation

Summary The development of a selective and sensitive HPLC method for the determination of semipermanent hair colorants in cosmetic formulations is proposed. The separation and identification of N-hydroxyalkyl nitrophenylenediamines and nitroaminophenols were performed by HPLC with on-line, post-column, photochemical derivatisation, using a reversed phase, ion-pair system with 1,8-diaminooctane and heptansulfonate in the mobile phase. Two UV spectra (photoreactor on and off) were obtained for each analyte, adding information for confirming peak identity. Analyte-modified spectral properties were used to increase the method sensitivity. The proposed method was successfully applied to quality control and stability studies of cosmetic formulations.     

Development of nanoformulation for hyperpigmentation disorders: Experimental evaluations,in vitro efficacy and in silico molecular docking studies

Hyperpigmentation is a crucial dermatological disorder. This study aims to formulate a nanoemulsion formulation containing chlorogenic acid (CA) for hyperpigmentation treatment, to carry out characterization studies, and to investigate its efficacy and safety in vitro and in silico analysis.In line with this purpose, CA nanoemulsions (CA-NEs) were developed using the ultrasonic homogenization method. Accelerated stability tests were performed to examine the kinetic and thermodynamic stability of the CA-NEs to ascertain the presence of any stability issues. After the heating–cooling test, appropriate CA-NEs were stored for 60 days in three different stability environments to examine the physicochemical stability and determine the finalized formulation. The toxicity of the finalized CA-NE formulation was evaluated by genotoxicity/mutagenicity and cytotoxicity tests. The tyrosinase and melanogenesis activities of the finalized CA-NE formulation were determined on the Melanoma B16F0 cell line. Finally, the molecular docking method was used to reveal interactions of CA that play an essential role in tyrosinase inhibition. Additionally, the mushroom and human tyrosinase enzymes were used to determine the activity of CA. In addition, the comparison study with the molecular docking method was carried out using kojic acid as a reference molecule.In conclusion, the molecular docking study, pharmacokinetic analyses, and in vitro studies showed that F4P1 coded CA-NE formulation might hold promise as an innovative formulation in cosmetic applications such as skin-lightening effects with its high efficacy and safety profile.     

Physical Stability and the Droplet Distribution of Rice Oil–in–Water Emulsion

The objective of the current study was to evaluate long-term stability of emulsions with rice oil by assessing their physical properties. For this purpose, six emulsions were prepared, their stability was examined empirically, and the most correctly formulated emulsion composition was determined using a computer simulation. Variable parameters (oil and thickener content) were indicated with optimization software based on Kleeman's method. Synthesized emulsions were studied by numerous techniques involving determination of particle size and distribution of emulsion, optical microscopy, viscosity, and novelty analysis—Turbiscan test.

The emulsion containing 50 g of oil and 1.2 g of thickener had the highest stability. Empirically determined parameters proved to be consistent with the results obtained using the computer software. The computer simulation showed that the most stable emulsion should contain from 35.93 to 50 g of oil and 0.94 to 1.19 g of thickener. The computer software based on Kleeman's method proved to be useful for fast optimization of the composition and providing parameters of stable emulsion systems. Forming emulsions based on rice oil is a chance to introduce a new, interesting representative of functional food as well as a cosmetic product.