PVP solid dispersions containing Poloxamer 407 or TPGS for the improvement of ursolic acid release

Abstract Solid dispersions (SDs) of ursolic acid (UA) were developed using polyvinylpyrrolidone K30 (PVP K30) in combination with non-ionic surfactants, such as D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) or poloxamer 407 (P407) with the aim of enhancing solubility and in vitro release of the UA. SDs were investigated using a 24 full factorial design, subsequently the selected formulations were characterized for water solubility, X-ray diffractometry (XRD), differential scanning calorimetry (DSC), particle diameter, scanning electron microscopy, drug content, physical-chemical stability and in vitro release profile. SDs showed higher UA water-solubility than physical mixtures (PMs), which was attributed by transition of the drug from crystalline to amorphous or molecular state in the SDs, as indicated by XRD and DSC analyses. SD1 (with P407) and SD2 (with TPGS) were chosen for further investigation because they had higher drug load. SD1 proved to be more stable than SD2, revealing that P407 contributed to ensure the stability of the UA. Furthermore, SD1 and SD2 increased UA release by diffusion and swelling-controlled transport, following the Weibull model. Thus, solid dispersions obtained with PVP k-30 and P407 proved to be advantageous to enhance aqueous solubility and stability of UA.

Insulin-loaded polymeric mucoadhesive nanoparticles: development, characterization and cytotoxicity evaluation

Abstract Mucoadhesive nanoparticles are particularly interesting for delivery through nasal or pulmonary routes, as an approach to overcome the mucociliary clearance. Moreover, these nanoparticles are attractive for peptide and protein delivery, particularly for insulin to treat diabetes, as an alternative to conventional parenteral administration. Thus, chitosan, a cationic mucoadhesive polysaccharide found in shells of crustaceans, and the negatively-charged dextran sulfate are able to form nanoparticles through ionic condensation, representing a potential insulin carrier. Herein, chitosan/dextran sulfate nanoparticles at various ratios were prepared for insulin loading. Formulations were characterized for particle size, zeta potential, encapsulation efficiency, scanning electron microscopy, differential scanning calorimetry, and in vitro drug release. Moreover, the interaction with mucin and the cytotoxicity against a lung cell line were studied, which altogether have not been addressed before. Results evidenced that a proper selection of polyelectrolytes is necessary for smaller particle size formation and also the composition and zeta potential impact encapsulation efficiency, which is benefited by the positive charge of chitosan. Insulin remained stable after encapsulation as evidenced by calorimetric assays, and was released in a sustained manner in the first 10 h. Positively-charged nanoparticles based on chitosan/dextran-sulfate at the ratio of 6:4 successfully interacted with mucin, which is a prerequisite for delivery to mucus-containing tissues. Finally, insulin-loaded nanoparticles displayed no cytotoxicity effect against lung cells at tested concentrations, suggesting the potential for further in vivo studies.

Organic cocoa extract -loaded surfactant-based systems intended to skin bioadhesion

ABSTRACT This study was to develop, characterize, and evaluate the physical-chemical stability, in vitro antioxidant activity and in vitro safety profile of liquid crystalline systems (LCS) and microemulsions (MEs) with and without organic cocoa (OC) extract. LCS stabilized by surfactant polyoxyethylene 20 cetyl ether, containing water and oleic acid were studied. LCS and MEs were characterized using polarized light microscopy, small angle X-ray scattering, rheology and in vitro bioadhesion, and were evaluated for a period of 30 days by visual aspects, centrifuge test, pH value and relative density. PLM and SAXS assays showed the presence of domains of MEs, cubic and hexagonal mesophasephases, varying the proportions of the components of the formulations; where in the addition of the extract did not change rheological behavior of the formulations. All of the formulations were stable in the period analyzed and presented higher bioadhesive strength. In vitro antioxidant activity suggests that LCS and MEs presented a high capacity to maintain the antioxidant activity of OC extract. The results showed that the incorporation of OC in LCS improved the safety profile, according to cytotoxicity assays of systems may be a promising platform to OC extract for topical application for the potential treatment of skin disorders.

Green tea glycolic extract-loaded liquid crystal systems: development, characterization and microbiological control

ABSTRACT Liquid crystal systems (LCSs) have interesting cosmetic applications because of their ability to increase the therapeutic efficiency and solubility of active ingredients. The aim of the present research was to develop green tea glycolic extract-loaded LCSs, to characterize and to perform microbiological control. The ternary phase diagram was constructed using polysorbate 20, silicone glycol copolymer (SGC) - DC 193(r), and distilled water with 1.5% glycolic green tea extract. The systems were characterized by polarized light microscopy. Formulations selected were characterized as transparent viscous systems and transparent liquid system indicated mesophases lamellar structure. The results of the microbiological analysis of mesophilic aerobic microorganisms (bacteria and fungi) revealed that the above formulation showed a biologic load <10 CFU/mL in all samples. In conclusion, liquid crystalline systems that have presented formation of a lamellar mesophases were developed. Furthermore, the formulation and products tested presented the adequate microbiological quality in accordance with official recommendations.

Development of nanotechnology-based drug delivery systems with olive vegetable oil for cutaneous application

ABSTRACT Liquid-Crystalline Systems represent active compounds delivery systems that may be able to overcome the physical barrier of the skin, especially represented by the stratum corneum. To obtain these systems, aqueous and oily components are used with surfactants. Of the different association structures in such systems, the liquid-crystalline offer numerous advantages to a topical product. This manuscript presents the development of liquid-crystalline systems consisting, in which the oil component is olive oil, its rheological characterizations, and the location of liquid crystals in its phase map. Cytotoxic effects were evaluated using J-774 mouse macrophages as the cellular model. A phase diagram to mix three components with different proportions was constructed. Two liquid crystalline areas were found with olive oil in different regions in the ternary diagram with two nonionic surfactants, called SLC1 (S1) and SLC2 (S2). These systems showed lamellar liquid crystals that remained stable during the entire analysis time. The systems were also characterized rheologically with pseudoplastic behavior without thixotropy. The texture and bioadhesion assays showed that formulations were similar statistically (p < 0.05), indicating that the increased amount of water in S2 did not interfere with the bioadhesive properties of the systems. In vitro cytotoxic assays showed that formulations did not present cytotoxicity. Olive oil-based systems may be a promising platform for skin delivery of drugs.

RESUMO Os cristais líquidos representam um sistema de liberação de substâncias ativas capazes de vencer a barreira cutânea, representada especialmente pelo estrato córneo. Água, óleo e tensoativos são misturados para se obter esses sistemas. Diferentes estruturas podem ser formadas nesses sistemas, as quais oferecem muitas vantagens para os produtos de uso tópico. Esse trabalho visou ao desenvolvimento de sistemas líquido-cristalinos preparados com óleo de oliva, sua caracterização reológica e a identificação das fases cristalinas no diagrama ternário. Efeitos citotóxicos foram avaliados usando células de rato como modelo celular. Construiu-se um diagrama de fases que mistura três componentes em diferentes proporções. Duas áreas de cristal líquido, denominadas SLC1 (S1) e SLC2 (S2), foram encontradas com óleo de oliva em diferentes regiões no diagrama ternário preparado com dois diferentes tensoativos não-iônicos. Esses sistemas mostraram fase cristalina lamelar, que permaneceu estável durante o tempo estudado. Os sistemas foram também caracterizados reologicamente e apresentaram comportamento pseudoplástico com tixotropia. Os ensaios de textura e bioadesão mostraram que as formulações foram similares (p < 0.05), indicando que o aumento da quantidade de água em S2 não interferiu nas propriedades bioadesivas dos sistemas. Os ensaios de citotoxicidade mostraram que as formulações não foram citotóxicas. Sistemas à base de óleo de oliva são interessantes para a liberação de fármacos na pele.

Sustainability, natural and organic cosmetics: consumer, products, efficacy, toxicological and regulatory considerations

The interest in sustainable products has increased along the years, since the choice of products, packaging and production processes have a great impact on the environment. These products are classified by regulatory agencies in different categories, aggregating advantages to the product and increasing the demand by consumers. However, there is no harmonization in guidelines of these certifying agencies and each cosmetic industry formulates their product and packaging in a more rational way, which causes less damage to the environment. Many cosmetic products have in their formulation natural products that perform a specific biological function, but these products should be evaluated on efficacy and toxicological aspects. The aim of this article is to approach sustainability, natural and organic cosmetics, considering the consumer and the efficacy, toxicological and regulatory aspects.

O interesse por produtos sustentáveis tem aumentado ao longo dos anos, desde a escolha dos produtos, embalagens e processos de produção tendo um grande impacto sobre o meio ambiente. Estes produtos são classificados por agências reguladoras em diferentes categorias, agregando vantagens ao produto e aumentando a demanda por parte dos consumidores. No entanto, não existe uma harmonização nas diretrizes destes órgãos de certificação e cada indústria cosmética formula seu produto e embalagem de uma forma mais racional, levando a menos danos ao meio ambiente. Muitos produtos cosméticos têm produtos naturais na formulação que executam uma função biológica específica, porém estes produtos devem ser avaliados quanto a sua eficácia e toxicidade. O objetivo deste artigo é abordar a sustentabilidade, cosméticos naturais e orgânicos, considerando os aspectos regulatórios, do consumidor e os aspectos de eficácia e toxicológicos.

Validation of high-performance liquid chromatographic method for analysis of fluconazole in microemulsions and liquid crystals

In recent decades, there has been a significant increase in the incidence of fungal diseases. Certain fungal diseases cause cutaneous lesions and in the usual treatment, generally administred orally, the drug reaches the site of action with difficulty and its concentration is too low. An approach much explored in recent years is the development of nanotechnology-based drug delivery systems, and microemulsions (ME) and liquid crystals (LC) are promising. ME and LC were developed with oleic acid or copaiba oil as the oil phase, propoxyl (5OP) ethoxyl (20 OE) cetyl alcohol as surfactant and water. An analytical method to assess the incorporation of fluconazole (FLU) in the systems under study was validated according to guidelines of the International Conference on Harmonization (ICH) guidelines and the Brazilian Food, Drug and Sanitation Agency (ANVISA). The method was conducted on a C18-RP column (250 × 4.6 mm i.d.), maintained at room temperature. The mobile phase consisted of acetonitrile and water (50:50, v/v), run at a flow rate of 1.0mL/min and using ultraviolet detection at 210nm. The chromatographic separation was obtained with a retention time of 6.3min, and was linear in the range of 20-400 µg/mL (r2=0.9999). The specificity showed no interference of the excipients. The accuracy was 100.76%. The limits of detection and quantitation were 0.057 and 0.172 µg.mL-1, respectively. Moreover, method validation demonstrated satisfactory results for precision and robustness. The proposed method was applied for the analysis of the incorporation of FLU in ME and LC, contributing to improve the quality control and to assure the therapeutic efficacy.

Nas últimas décadas, houve aumento significativo na incidência de doenças fúngicas. Certas doenças fúngicas provocam lesões cutâneas, sendo que no tratamento usual, geralmente administrado por via oral, o medicamento chega ao local de ação com dificuldade, em concentração muito baixa. Uma abordagem muito explorada nos últimos anos é o desenvolvimento de sistemas de administração de fármacos baseados em nanotecnologia, como as microemulsões (ME) e cristais líquidos (LC). ME e LC foram desenvolvidos com o ácido oleico ou óleo de copaíba como fase oleosa, álcool cetílico propoxilado (5 OP) e etoxilado (20 OE) como tensoativo e água. Método analítico para avaliar a incorporação de fluconazol (FLU) nos sistemas em estudo foi validado de acordo com as diretrizes da Conferência Internacional de Harmonização (ICH) e Agência Nacional de Vigilância Sanitária (ANVISA). O método foi desenvolvido empregando coluna C18-RP (250 x 4,6 mm id), mantida à temperatura ambiente. A fase móvel consistiu de acetonitrila e água (50:50, v/v), executado a uma taxa de fluxo de 1,0 mL/min e com detecção ultravioleta a 210 nm. A separação cromatográfica foi obtida com o tempo de retenção de 6,3min, e mostrou-se linear no intervalo de 20-400 µg/mL (r2=0,9999). Pelo estudo de especificidade, observou-se não interferência dos excipientes. A precisão foi 100,76%. Os limites de detecção e de quantificação foram 0,057 e 0,172 µg.mL-1, respectivamente. Além disso, a validação do método demonstrou resultados satisfatórios para a precisão e robustez. O método proposto foi aplicado para a análise da incorporação do FLU em ME e cristais líquidos, contribuindo para aumentar o controle de qualidade e garantir a eficácia terapêutica.

Atividade antioxidante do extrato seco de cacau orgânico (Theobroma cacao) - estudo de estabilidade e teste de aceitação de cremes acrescidos deste extrato / Antioxidant activity of organic cocoa dried extract (Theobroma cacao), stability study and acceptance testing of cosmetic cream containing this extract

Os frutos de cacau (Theobroma cacao) são conhecidos mundialmente pela sua riqueza em ácidos graxos e compostos fenólicos com poder antioxidante, sendo que em sua constituição é possível relatar mais de 50% em ácidos graxos de cadeia média que o torna matéria-prima passível de ser explorada pela indústria alimentícia, farmacêutica e cosmética. Este trabalho teve como objetivo estudar o poder antioxidante do extrato seco de cacau orgânico, obter formulações cosméticas acrescidas deste extrato, promovendo os estudos de estabilidade, ensaios reológicos e a investigação de cristais-líquidos, bem como realizar o teste de aceitação das mesmas. O extrato vegetal foi avaliado quanto seu poder antioxidante pelo método de sequestro radicalar DPPH. Formulações cosméticas foram obtidas e amostras foram submetidas a ensaios físico-químicos de estabilidade (caracterização organoléptica, teste de centrífuga e determinação dos valores de pH), caracterização reológica, assim como análises em microscopia de luz polarizada. As preparações estáveis também foram avaliadas quanto a sua aceitabilidade por provadores. A partir dos resultados apresentados pôde-se constatar a atividade antioxidante do extrato seco de cacau orgânico e obter preparações cosméticas, constituídas deste ativo a 5%, com comportamento pseudoplástico associado à tixotropia e providas de cristais líquidos lamelares. Verificou-se também que a concentração de cera autoemulsionante interferiu na aceitação do produto cosmético.

The cocoa fruit (Theobroma cacao) is known worldwide for its richness in fatty acids and phenolic compounds, with antioxidant power, and it is known to be composed of more than 50% medium-chain fatty acids, making it a raw material that could be exploited by the food, pharmaceutical and cosmetics industries. the aim of this study was to assess the antioxidant power of organic cocoa dried extract, to develop cosmetic formulations from this extract and to determine their stability and carry out rheological tests, liquid-crystal research and acceptance testing on them. the plant extract was assayed for its antioxidant power by the DPPH radical scavenging method. Cosmetic formulations were produced and samples were subjected to physicochemical stability tests (organoleptic assessment, centrifugal testing and determination of pH), rheological characterization and polarized light microscopy analysis. the stable preparations were also evaluated for their acceptability by consumers. From the results presented, it was possible to characterize the antioxidant activity of dried organic cocoa extract and to prepare cosmetic preparations containing 5% of this active compound. these showed pseudoplastic behavior associated with thixotropy and lamellar liquid crystals were presentat all storage times and temperatures. It was also found that the higher self-emulsifying wax contents interfered with consumer acceptance of the cosmetic product.

Development, physical-chemical stability and rheological behavior of silicones formulations containing Dimethylaminoethanol (DMAE).

The aim of this paper was to develop formulations increased of DMAE and evaluate their physical-chemical stability and rheological behavior. Eleven formulations containing 3% DMAE pidolate or 3% DMAE acetamidobenzoate were developed and both preliminary stabilities tests and rheological measurements were carried out. They were considered stable during all period of study. The type of DMAE did not modify the viscosity of the emulsion and all presented pseudoplastic behavior with hysteresis area. An increase of hysteresis area could be observed with DMAE addition. The results point that the type of DMAE can influence the physical stability of the final product.

Evaluation of skin hydration after exposition to the aqueous and hydroalcoholic bases and silicone emulsion.

Several dermocosmetic bases even without active substances, can increase the cutaneous hydration, resulting in a beneficial effect to the skin. The evidence and interpretation of possible hydration effect of formulations in the skin can be carried through by means of histopathological and histomorphometrical evaluation, a time that allows the analysis of the epithelial tissue, of dermis and also of the cellular characteristics. The objective of this research was to evaluate the skin hydration after exposition to the aqueous and hydroalcoholic bases and silicone emulsion. Swines had areas submitted to treatments during 15 days with three different formulations (F1 - aqueous gel, F2 - hydroalcoholic gel and F3 - silicone emulsion). By means of histometric and histopathological techniques were gotten the thickness of the epidermis and stratum corneum. Comparison of means was done using ANOVA followed by the Tukey test. The F1 provoked significant increase in the thickness of the epidermis. The formulaton F2 provoked significant reduction in the thickness of the epidermis and stratum corneum. F3 not presented significant difference in this structures. According to the study, the type of base chosen intervenes with the skin hydration.