N,N,N-trimethylchitosan-poly (n-butylcyanoacrylate) core-shell nanoparticles as a potential oral delivery system for acyclovir.

This study investigated the feasibility of polysaccharide-coated poly(n-butyl cyanoacrylate) (PBCA) nanoparticles for oral delivery of acyclovir (ACV). PBCA nanoparticles were obtained by the emulsion polymerization method. Chitosan was chemically modified to obtain N,N,N-trimethylchitosan (TMC), which was used to coat the nanoparticles (PBCA-TMC). Nanoparticles were characterized by dynamic light scattering, zeta potential, differential scanning calorimetry (DSC), atomic force microscopy (AFM), cytotoxicity, and the effect on the transepithelial electrical resistance (TEER) of the Caco-2 cells. The size of the coated nanoparticles (296.2 nm) was significantly larger than uncoated (175.0 nm). Furthermore, PBCA nanoparticles had a negative charge (-11.7 mV), which was inverted to highly positive values (+36.5 mV) after coating. DSC analysis suggested the occurrence of the coating, which was confirmed by AFM images. The MTT assay revealed concentration-dependent cytotoxicity for the core-shell nanoparticles. Additionally, PBCA-TMC caused a significant but reversible decrease in the Caco-2 cell monolayer TEER. Entrapped ACV (PBCA-ACV-TMC), a Biopharmaceutical Classification System class III drug substance, increased approximately 3.25 times the Papp of ACV in the Caco-2 permeability assay. The nanoparticles were also able to provide in vitro ACV controlled release using media with different pH values (1.2; 6.8; 7.4). Accordingly, this new core-shell nanoparticle showed the potential to improve the oral delivery of ACV.

Validation Cytotoxicity Assay for Lipophilic Substances.

It is challenging to disperse lipophilic substances in a validated cytotoxicity assay, especially for compounds with log Kow greater than or equal to 5 that may show false negative results. The purpose of this study was to explain the challenges in conducting a cytotoxicity validated test of lipophilic substances: Minthostachys setosa, Pimenta pseudocaryophyllus, and Drimysbrasiliensis essential oils. Additionally, we compared the equivalence of Neutral Red (NR) and 3- (4,5-dimethylthiazol-2-yl) -5- (3- carboxymethoxyphenyl) -2- (4-sulfophenyl) -2H -tetrazolium, inner salt (MTS) in detecting cell viability. The Hydrophile-Lipophile Balance (HLB) technique was used to evaluate the dispersion of essential oils and cytotoxicity in accordance to the guidelines of the OECD / GD 129 validated cytotoxicity assay. We compared the equivalence of vital dyes by TOST equivalence test. According to the results, we demonstrated the possibility of using other ways to disperse the lipophilic substances. Based on the HLB theory, we selected polysorbate 20 as the best solubilizing agent of the essential oils studied in D10 culture medium.

Quality by design (QbD), Process Analytical Technology (PAT), and design of experiment applied to the development of multifunctional sunscreens.

Multifunctional formulations are of great importance to ensure better skin protection from harm caused by ultraviolet radiation (UV). Despite the advantages of Quality by Design and Process Analytical Technology approaches to the development and optimization of new products, we found in the literature only a few studies concerning their applications in cosmetic product industry. Thus, in this research work, we applied the QbD and PAT approaches to the development of multifunctional sunscreens containing bemotrizinol, ethylhexyl triazone, and ferulic acid. In addition, UV transmittance method was applied to assess qualitative and quantitative critical quality attributes of sunscreens using chemometrics analyses. Linear discriminant analysis allowed classifying unknown formulations, which is useful for investigation of counterfeit and adulteration. Simultaneous quantification of ethylhexyl triazone, bemotrizinol, and ferulic acid presented at the formulations was performed using PLS regression. This design allowed us to verify the compounds in isolation and in combination and to prove that the antioxidant action of ferulic acid as well as the sunscreen actions, since the presence of this component increased 90% of antioxidant activity in vitro.

Hydrolyzed collagen interferes with in vitro photoprotective effectiveness of sunscreens

ABSTRACT The chronological skin aging is a progressive and natural process with genetic and physiological changes. However, ultraviolet (UV) radiation may accelerate the oxidative stress, generating carcinogenesis and photoaging. Natural compounds and their applications are considered a trend in the cosmetic market. The protein-based film-forming compounds play an important role, once it collaborates for the better distribution of sunscreens on the skin. Here we investigated the in vitro photoprotective effectiveness of sunscreens containing the hydrolyzed collagen associated with UVA, UVB and/or inorganic filters. Sunscreens were developed with octocrylene (7.5%), butyl methoxydibenzoylmethane (avobenzone) (3.0%) and/or titanium dioxide (5.0%), associated or not with the hydrolyzed collagen (3.0%). In vitro photoprotective effectiveness was determined in a Labsphere(r) UV2000S by the establishment of the sun protection factor (SPF) and critical wavelength (nm) values. Physicochemical and organoleptic characteristics were also assayed. The hydrolyzed collagen subjectively improved the formulation sensory characteristics. However, this bioactive compound led to a decrease of the SPF values of the photoprotective formulations containing octocrylene alone and octocrylene + butyl methoxydibenzoylmethane + TiO2. This inadequate interaction may be considered during the development of new sunscreens intended to contain protein-based components.

Gelatin-based microspheres crosslinked with glutaraldehyde and rutin oriented to cosmetics

ABSTRACT Glutaraldehyde (GTA) has been extensively used as a gelatin crosslinking agent, however, new natural ones have been suggested as more biocompatible. Polyphenols are possible candidates and the flavonols, such as rutin (RUT), also exhibit potential synergism with sunscreens and antioxidant agents used in cosmetics. In this work, gelatin microspheres (M0) were obtained and crosslinked with GTA 10 mM (MG) or RUT 10 mM (MR), dissolved in acetone:NaOH 0,01M (70:30 v/v). MG exhibited crosslinking extent of 54.4%. Gelatin, M0, MG and MR did not elicit any signs of skin damage, regarding the formation of erythema, the barrier function disruption and negative interference in the stratum corneum hydration. Oily dispersions containing M0, MG or MR, isolated or combined with benzophenone-3 or octyl methoxycinnamate, suggested that the microspheres, at a 5.0% w/w, had no additional chemical or physical photoprotective effect in vitro. Crosslinking with RUT had occurred, but in a lower degree than GTA. Microspheres had not improved sun protection parameters, although, non-treated gelatin interfered positively with the SPF for both UV filters. The in vivo studies demonstrated that these materials had very good skin compatibility.

Particle size and morphological characterization of cosmetic emulsified systems by Optical Coherence Tomography (OCT)

ABSTRACT The physicochemical attributes of emulsified systems are influenced by the characteristics of their internal phase droplets (concentration, size and morphology), which can be modified not only by the formulation components, but also by the analytical methodology employed. Thus, the aim of this work involved the physicochemical characterization of cosmetic emulsions obtained from different surfactants, as well as the introduction of the optical coherence tomography (OCT) as the analytical technique employed for the morphological characterization and particle size determination of the formulations. Three emulsions were prepared, differing at the type and concentration of the surfactant used, and their droplet sizes were evaluated through optical microscopy, laser diffraction and OCT. The microscopic analysis and the laser diffraction techniques provided an average particle size minor than 6.0 µm, not detected by the OCT technique, which could identify only bigger particles of the emulsified systems' internal phase. The results testify that OCT was suitable for the morphological characterization of cosmetic emulsions; however, the technique needs to be improved to ensure a better sensitivity in the analysis of smaller particles.

RESUMO Os atributos físico-químicos de sistemas emulsionados são influenciados pelas características de suas gotículas de fase interna (concentração, tamanho e morfologia), as quais podem ser modificadas não apenas pelos componentes da formulação, mas também pela metodologia analítica empregada. Desta forma, o objetivo deste trabalho envolveu a caracterização físico-química de emulsões cosméticas obtidas a partir de diferentes tensoativos, bem como a introdução da tomografia de coerência óptica (OCT) como a técnica analítica utilizada para a caracterização morfológica e determinação do tamanho de partícula das formulações. Três emulsões foram preparadas, diferindo no tipo e concentração do tensoativo empregado, e seus tamanhos de gotícula foram avaliados por meio das técnicas de microscopia óptica, difração a laser e OCT. As técnicas de microscopia óptica e difração a laser forneceram tamanhos de partícula médios menores de 6.0 µm, não detectados pela técnica de OCT, que permitiu apenas a identificação de partículas maiores pertencentes à fase interna dos sistemas emulsionados. Os resultados reforçam a introdução da OCT como metodologia promissora para a caracterização morfológica de emulsões cosméticas; no entanto, a técnica requer aprimoramento para garantir maior sensibilidade na análise de partículas de menor tamanho.

Functional photostability and cutaneous compatibility of bioactive UVA sun care products.

Sunscreens are the most-established approach for photoprotection. The strategy of providing antioxidant properties to sun care products by addition of natural and potent anti-free radical compounds has led to the development of bioactive sunscreens, able to neutralize the harmful effects of ultraviolet (UV) radiation. UVA filters, such as benzophenone-3 (BP) and butyl methoxydibenzoylmethane (BMDBM), can exhibit photodegradation which limits the development of broad spectrum sunscreens. Previous research verified that rutin interacts with filters incorporated in sunscreens. In this work, we focused on the development and evaluation of the efficacy of the sunscreens containing either BP or BMDBM with and without rutin. The addition of rutin to the UVA filters afforded antioxidant properties to the formulations and they were considered safe for human use. Additionally, rutin in combination with either BP or BMDBM increased the antioxidant activity about 40 times when compared with the UVA filters alone. Remarkably, the addition of rutin 0.1% (w/w) to BP 6.0% (w/w) raised the SPF from 24.3±1.53 to 33.3±2.89. In conclusion, these findings demonstrated that the addition of rutin into sunscreens can markedly improve the antioxidant properties of the formulation as well as photostabilize some of the UVA filters.

Development of ciclopirox olamine topical formulations: evaluation of drug release, penetration and cutaneous retention.

With the aim of reducing system absorption and consequently, the side effects, and simultaneously select a penetration enhancing, three topical formulations with 0.5% ciclopirox olamine (CO) and 15% of propylene glycol (PG), ethoxydiglycol or oleic acid were developed and evaluated regarding the skin penetration and cutaneous retention of the drug using Franz diffusion cells. Release experiments were performed through synthetic membrane while dermatomed pig ear skin was used to evaluate CO skin penetration and skin retention. Retention studies were carried out applying tape stripping method and dosing CO in stratum corneum and in epidermis and dermis. A HPLC method was validated for quantifying CO. All formulations tested with synthetic membrane presented no retention of the drug. Permeation data suggested that there was no systemic absorption of ciclopirox olamine from the studied formulations, even when the skin penetration enhancers were applied. Higher concentrations of the drug were found in the stratum corneum (SC) and also in epidermis and dermis, for all of the developed formulations. The addition of enhancers improved the penetration and cutaneous retention of CO, and propylene glycol promoted higher concentrations in epidermis and dermis, probably because its cumulative effect on the skin and by an efficient solvent power.

Reverse phase high-performance liquid chromatography for quantification of hydroxymethylnitrofurazone in polymeric nanoparticles

Hydroxymethylnitrofurazone (NFOH) is a new compound with potential leishmanicidal and trypanocidal activity. Despite its effectiveness, the formulators have to overcome its poor aqueous solubility. Recently, polymeric nano-scale drug delivery systems have proposed for the treatment of neglected diseases. As several studies have confirmed the advantages of such formulations, and this approach provides new analytical challenges, including the need to detect trace amounts of the drug. A suitable method was developed and validated for NFOH determination bound to poly (n-butylcyanoacrylate) (PBCA) nanoparticles. The chromatographic separation was achieved using a C18 column maintained at 25 ºC and an isocratic mobile phase consisting of water and acetonitrile: 80:20 (v/v) at a flow rate of 1.2 mL min-1 and UV-detection at 265 nm. Investigated validation parameters included selectivity, linearity, accuracy, precision and robustness (changes in column temperature, mobile phase composition and flow). The method was specific, the peak of NFOH had no interference with any nanoparticle excipients and no co-elution with main degradation product (nitrofurazone). Linearity was over the range of 0.94 13.11 μg mL-1 (r2=0.999). The method was accurate and precise, recovery of 100.7%, RSD of 0.4%; intra-day and inter-day RSD range 9.98-9.99 μg mL-1 and 0.3% to 0.5%, respectively. Robustness confirmed that method could resist the applied changes. Application of the optimized method revealed an encapsulation efficiency of 64.4% (n=3). Therefore, the method was successfully developed and validated for the determination of the encapsulation efficiency of NFOH-PBCA nanoparticles.

Hidroximetilnitrofural (NFOH) é um novo composto que possui atividade leishmanicida e tripanomicida potencial. Um método apropriado foi desenvolvido e validado para a determinação de NFOH em nanopartículas de poli(n-butil cianoacrilato) (PBCA). A separação cromatográfica foi obtida usando uma coluna C18 (5 µm de tamanho de partícula, 4,6 mm de diâmetro e 150 mm de comprimento), mantida a 25 °C, fase móvel composta de água e acetonitrila 80:20 (v/v), fluxo de 1,2 mL min- 1 e detecção por UV a 265 nm. Investigaram-se os seguintes parâmetros de validação: seletividade, linearidade, exatidão, precisão e robustez (mudanças na temperatura de coluna, proporção da fase móvel e fluxo). O método mostrou-se específico, o pico de NFOH não apresentou interferência dos picos provenientes dos excipientes das nanopartículas e separado do principal produto de degradação (nitrofural). A linearidade foi obtida na faixa de 0,94-13,11 μg mL- 1 (r2=0,999). O método mostrou exatidão (recuperação de 100,7%, DPR de 0,4 %) e precisão (intra-dia e inter-dia, 9,98-9,99 μg mL- 1 e DPR 0,3% a 0,5%, respectivamente). A robustez provou que o método pode resistir às mudanças propostas. Aplicação do método otimizado revelou eficiência de encapsulação de 64,4% (n=3). Portanto, o método foi desenvolvido e validado com sucesso para a determinação da eficiência de encapsulação de nanopartículas de NFOH-PBCA.

Avaliação do fator de proteção solar (FPS) in vitro e perfil reológico de fotoprotetores comerciais infantis / Assessment of in vitro Sun Protection Factor (SPF) and rheological profile of commercial infant sunscreens

A pesquisa tem como objetivo a aplicação da transmitância espectral utilizando uma esfera de integração para estimar o Fator de Proteção Solar (FPS) de fotoprotetores comerciais para o uso infantil. Fotoprotetores com FPS 30 (A, B e C), disponíveis comercialmente, foram selecionados para avaliação conforme as seguintes metodologias: valor de pH, perfil reológico, e valor de FPS in vitro por espectroscopia. As amostras A, B e C apresentaram, respectivamente, os seguintes valores de pH: 7.8, 7.4 e 7.0. O perfil reológico identificou os sistemas como semissólidos pseudoplásticos não-Newtonianos, com área de histerese. O teste-T (p < 0.05) foi utilizado para confrontar o FPS alegado (FPS = 30) com o estimado por espectroscopia. Estudos in vitro foram considerados de grande importância para a área cosmética, podendo corroborar, previamente, a realização dos estudos de eficácia in vivo. De acordo com os resultados, as amostras A, B e C apresentaram valores de FPS sem diferença estatisticamente significativa, quando comparados àqueles citados nos rótulos. A transmitância espectral utilizando esfera de integração provou ser uma metodologia conveniente, rápida e reprodutível para a avaliação estimada do FPS.

This research focused on the measurement of spectral transmittance using an integrating sphere to estimate the Sun Protection Factor (SPF) of commercial sunscreens oriented for child use. Commercially available SPF 30 sunscreens (A, B and C) were selected and assessed by the following methodology: pH measurement; rheological profile analysis; and in vitro SPF estimation by spectroscopy. Samples A, B and C exhibited, respectively, pH values of 7.8, 7.4 and 7.0. The rheological profile identified the systems as pseudoplastic non-Newtonian semisolids with hysteresis loops. The t-test (p < 0.05) was used to confront the claimed SPF (SPF = 30) with that estimated by spectroscopy. In vitro tests are considered of utmost importance in the cosmetic , since their results may be used to validate submission to subsequent in vivo efficacy experiments. According to our results, sunscreens A, B and C generated SPF values without any significant difference from those claimed on the commercial sunscreen labels. The measurement of spectral transmittance with an integrating sphere proved to be a convenient, fast and reproducible method for SPF estimation.

Optimization of primaquine diphosphate tablet formulation for controlled drug release using the mixture experimental design.

A tablet formulation based on hydrophilic matrix with a controlled drug release was developed, and the effect of polymer concentrations on the release of primaquine diphosphate was evaluated. To achieve this purpose, a 20-run, four-factor with multiple constraints on the proportions of the components was employed to obtain tablet compositions. Drug release was determined by an in vitro dissolution study in phosphate buffer solution at pH 6.8. The polynomial fitted functions described the behavior of the mixture on simplex coordinate systems to study the effects of each factor (polymer) on tablet characteristics. Based on the response surface methodology, a tablet composition was optimized with the purpose of obtaining a primaquine diphosphate release closer to a zero order kinetic. This formulation released 85.22% of the drug for 8 h and its kinetic was studied regarding to Korsmeyer-Peppas model, (Adj-R(2) = 0.99295) which has confirmed that both diffusion and erosion were related to the mechanism of the drug release. The data from the optimized formulation were very close to the predictions from statistical analysis, demonstrating that mixture experimental design could be used to optimize primaquine diphosphate dissolution from hidroxypropylmethyl cellulose and polyethylene glycol matrix tablets.

Influence of particle size on appearance and in vitro efficacy of sunscreens

Nanotechnology applies to diverse sectors of science. In cosmetic area, investments have strengthened the idea that nanoproducts provide innumerable benefits to consumers. Extreme exposition to solar light can cause undesirable effects, thus, adding UV filters in cosmetic products are often used as prevention. Ethylhexyl methoxycinnamate and benzophenone-3 are UV filters widely used in sunscreen formulations, this UV filters absorb UVB and UVA radiation, respectively. In this study, sunscreen formulations were developed as nano and macroemulsion, but composed by the same raw material. Nanoemulsion was obtained by phase inversion temperature method (PIT). Physical and functional properties were evaluated by visual analysis, particle size distribution and by diffuse reflectance spectrophotometry. Achieved nanoemulsion showed bluish brightness aspect, less apparent consistency than macroemulsion, stability longer than 48 hours (22.0 ± 2.0 °C) and bimodal particle size distribution with average (mean) sizes around 10 nm (61%) and 4.5 µm (39%). Macroemulsion showed milky aspect, higher consistency than nanoemulsion, instability after 48 hours (22.0 ± 2.0 °C) and bimodal particle size distribution with average (mean) size around 202 nm (9%) and 10.4 µm (91%). Effectiveness profile of sunscreen formulations remained apparently similar, based on achieved results of in vitro SPF, UVA/UVB ratio and critical wavelength assays.

A nanotecnologia se aplica a diversos setores da ciência. Na área de cosméticos, os investimentos têm reforçado a idéia de que nanoprodutos oferecem inúmeros benefícios para os consumidores. A exposição excessiva à luz solar pode causar efeitos indesejáveis, logo, a adição de filtros UV em produtos cosméticos é frequentemente usada como prevenção. O p-metoxicinamato de octila e a benzofenona-3 são filtros UV amplamente utilizados em formulações de protecção solar, que absorvem radiações UVB e UVA, respectivamente. Neste estudo, desenvolveram-se formulações de protetores solares na forma de nano e macroemulsão, mas compostos pelas mesmas matérias-primas. A nanoemulsão foi obtida pelo método da temperatura de inversão de fases (PIT). As propriedades físicas e funcionais foram avaliadas por análise visual, distribuição de tamanho de partículas e por espectrofotometria de reflectância difusa. A nanoemulsão obtida apresentou brilho azulado, menor consistência aparente quando comparada `a macroemulsão, estabilidade superior a 48 horas (22,0 ± 2,0 ° C) e distribuição de tamanhos de partícula bimodal, com média (média) de tamanhos ao redor de 10 nm (61%) e 4,5 µm (39%) . A macroemulsão apresentou aspecto leitoso, maior consistência aaprente do que nanoemulsão, instabilidade após 48 horas (22,0 ± 2,0 ºC) e distribuição de tamanhos de partícula bimodal, com média (média) de tamanhos ao redor de 202 nm (9%) e 10,4 µm (91%). O perfil de eficácia das formulações fotoprotetoras permaneceu aparentemente similar, com base em resultados obtidos por ensaios de FPS in vitro, relação UVA/UVB e comprimento de onda crítico.

Using fluid bed granulation to improve the dissolution of poorly water-soluble drugs

In this study, fluid bed granulation was applied to improve the dissolution of nimodipine and spironolactone, two very poorly water-soluble drugs. Granules were obtained with different amounts of sodium dodecyl sulfate and croscarmellose sodium and then compressed into tablets. The dissolution behavior of the tablets was studied by comparing their dissolution profiles and dissolution efficiency with those obtained from physical mixtures of the drug and excipients subjected to similar conditions. Statistical analysis of the results demonstrated that the fluid bed granulation process improves the dissolution efficiency of both nimodipine and spironolactone tablets. The addition of either the surfactant or the disintegrant employed in the study proved to have a lower impact on this improvement in dissolution than the fluid bed granulation process.

Improvement of fluconazole flowability and its effect on dissolution from tablets and capsules / Melhoria da fluidez fluconazol e seu efeito sobre a dissolução de comprimidos e cápsulas

The aim of this work was to improve fluconazole flowability by wet granulation and to study the effect of granulation on drug dissolution from tablets and capsules. Fluconazole was submitted to a process of wet granulation in a high-speed granulator using Plasdone® K29/32 or K90. Flow properties of granules and dissolution profiles for tablets and capsules produced with them were determined. Fluconazole granules demonstrated better flowability, calculated by angle of repose and compressibility index data, compared with powder. Additionally, it was observed that the granulation process improved the dissolution efficiency (ED) of fluconazole from tablets and capsules, which could also suggest an increase in bioavailability. Higher dissolution efficiencies were achieved with Plasdone® K29/32.

O objetivo deste trabalho foi melhorar as características de fluxo do fluconazol com o emprego da granulação úmida e estudar o efeito desse processo na dissolução do fármaco em cápsulas e comprimidos. O fluconazol foi submetido ao processo de granulação úmida num granulador de alta velocidade empregando Plasdone K29/32 e K90. Foram determinadas as propriedades de fluxo dos grânulos e obtidos os perfis de dissolução de cápsulas e comprimidos obtidos com os granulados em estudo. Os grânulos de fluconazol apresentaram melhores características de fluxo após o processamento, demonstradas por meio das determinações do ângulo de repouso e do índice de compressibilidade, comparativamente à matéria-prima. Adicionalmente, observou-se que o processo de granulação melhorou a eficiência de dissolução (ED) do fluconazol nos comprimidos e cápsulas.

Spectroscopic and thermal characterization of alternative model biomembranes from shed skins of Bothrops jararaca and Spilotis pullatus / Caracterização espectroscópica e térmica de biomembranas modelo alternativo de peles galpão de Bothrops jararaca e Spilotis pullatus

Recently, there has been an interest in the use of shed snake skin as alternative model biomembrane for human stratum corneum. This research work presented as objective the qualitative characterization of alternative model biomembranes from Bothrops jararaca and Spilotis pullatus by FT-Raman, PAS-FTIR and DSC. The employed biophysical techniques permitted the characterization of the biomembranes from shed snake skin of B. jararaca and S. pullatus by the identification of vibrational frequencies and endothermic transitions that are similar to those of the human stratum corneum.

Existe atualmente interesse no uso da muda de pele de cobra como modelos alternativos de biomembranas da pele humana. O presente trabalho apresentou como objetivo a caracterização qualitativa de modelos alternativos de biomembranas provenientes de mudas de pele de cobra da Bothrops jararaca e Spilotis pullatus por espectroscopia Raman (FT-Raman), espectroscopia fotoacústica no infravermelho (PAS-FTIR) e calorimetria exploratória diferencial (DSC). As técnicas biofísicas FT-Raman, PAS-FTIR e DSC permitiram caracterizar qualitativamente os modelos alternativos de biomembranas provenientes das mudas de pele de cobra da B. jararaca e S. pullatus e identificar freqüências vibracionais e transições endotérmicas similares ao estrato córneo humano.

Physical and physicochemical stability evaluation of cosmetic formulations containing soybean extract fermented by Bifidobacterium animalis / Avaliação da estabilidade física e físico-química de formulações cosméticas contendo extrato de soja fermentado por Bifidobacterium animalis

Peel off facial masks, based on polyvinyl alcohol (PVA), are formulations that, after application and drying, form an occlusive film over the face. After removing, they provide cleanness, tensor and moisturizing effects, removing dead cells, residues and other materials deposited on the stratum corneous. The soybean extract fermented by Bifidobacterium animalis has sugars, amino acids, peptides, proteins and free isoflavonoids in high concentrations, when compared to the unfermented extract, providing benefits to the cosmetic formulations like anti-aging effect, moisture, tensor action and emollience. The cosmetic bases of peel off facial masks, added with 5.0 percent w/w of fermented soybean extract, were submitted to Preliminary and Accelerated Stability Studies. Eight (8) preparations were evaluated in several conditions of temperature (-10.0, 5.0, 22.0 and 45.0 ºC) and time (maximum of 15 days), comparing the results with the initial condition (48 h after preparation). The variables observed were: organoleptic characteristics, pH and appearing viscosity value and film drying time. The preparation containing 17.0 percent w/w of PVA and 0.5 percent w/w of guar gum was selected between the eight preparations initially prepared, because it presented the best performance in the stability test, being recommended storage at low temperatures (5.0 ºC).

As máscaras faciais peel off a base de álcool polivinílico (PVA) são formulações que, após a aplicação e secagem, formam um filme oclusivo sobre a face e, após sua remoção, conferem limpeza, ação tensora e hidratação à pele, retirando células mortas do estrato córneo, resíduos e outros materiais depositados. O extrato de soja fermentado por Bifidobacterium animalis possui açúcares, aminoácidos, peptídeos, e alto teor de isoflavonas na forma livre, quando comparado ao leite não fermentado, propiciando benefícios às formulações cosméticas, como ação antienvelhecimento, hidratação, efeito tensor e emoliência. As bases cosméticas de máscaras faciais peel off, acrescidas de extrato de soja fermentado 5,0 por cento p/p, foram submetidas aos ensaios de Estabilidade Preliminar e Acelerada, avaliando-se 8 preparações em diversas condições de temperatura (-10,0; 5,0; 22,0 e 45,0 ºC) e tempo (máximo de 15 dias), em relação à condição inicial (48 h após o preparo). As variáveis observadas envolveram: características organolépticas, valor de pH, viscosidade aparente e tempo de secagem do filme. A preparação contendo 17,0 por cento p/p de PVA e 0,5 por cento p/p de goma guar foi a selecionada dentre as oito preparações elaboradas inicialmente, por ter apresentado melhor desempenho no teste de estabilidade, sendo recomendado o armazenamento em temperatura reduzida (5,0 ºC).

Effects of caffeine and siloxanetriol alginate caffeine, as anticellulite agents, on fatty tissue: histological evaluation.

BACKGROUND: Cellulite is a physiological condition that presents etiologic plurality. Caffeine and its derivatives are used in anticellulite cosmetics due to their lipolytic activity on fatty cells. Siloxanetriol alginate caffeine (SAC) is a silanol derived from organic silicon. Radicals primarily from SAC are caffeine and the mannuronic acid. AIMS: This study aims to analyze the effects of caffeine and siloxanetriol alginate caffeine on fatty tissue by histological evaluation. METHODS: Formulations were developed with caffeine, caffeine + sodium benzoate or SAC and were applied topically for 21 days on Wistar female mice. The study regarded the histological aspects by determination of diameter and number of fatty cells with a light microscope. RESULTS: Emulsion with caffeine caused a reduction of 17% on the diameter of the fatty cells compared with the control. The emulsion with caffeine + sodium benzoate did not cause alterations on cell diameter. Emulsion with SAC provoked reduction on fatty cell diameters of 16%. No significant alterations were observed on the diameter of the fatty cells treated with gels, although it was noticed that gel with SAC promoted a reduction of 26% on the number of fatty cells. CONCLUSIONS: Emulsion with SAC was considered more indicated to promote the lipolytic action on fatty tissue, acting as a complement to treat cellulite. When sodium benzoate was added to the preparations, it inhibited the caffeine efficiency. Gel was not an adequate vehicle to be incorporated with caffeine and SAC.

Influence of cellulose polymers type on in vitro controlled release tablets containing theophylline

In this study, the effect of ethylcellulose (EC) and 6 types of hydroxypropylmethylcellulose (Methocel® K100M, K100MPRCR, K15MPRCR, K4MPRCR, K4M PR and E4MCR) on release profile of theophylline from matrix tablets was evaluated. Formulations tablets were prepared by either wet granulation or direct compression technique. The tablets were evaluated for physical characteristics and in vitro release of drug was performed as described in USP 30 ed. (Test 3). All formulations with cellulose polymer produced tablets easily and with physicals characteristics in accordance with official limits. Drug dissolution tests showed that formulations with 15 percent of Methocel® K4MPR, 15 percent of Methocel® K4MPRCR and 30 percent of Ethocel® N10STD, obtained by direct compression method, complied with official specifications, in terms of release profile and diffusion was the main mechanism involved in theophylline delivery.

Os efeitos das variáveis das formulações na liberação da teofilina a partir da hidroxipropilmetilcelulose (HPMC) e etilcelulose (EC) em comprimidos matriciais foram estudados. Formulações de comprimidos foram preparadas pelos métodos da granulação úmida ou compressão direta usando diferentes viscosidades de HPMC. Propriedades físico-químicas dos comprimidos e liberação do fármaco foram estudadas conforme dissolução descrita no Teste 3 da Farmacopéia Americana 30ed. Ensaios "in vitro" mostraram que as formulações com 15 por cento de Methocel® K4MPR, 15 por cento de Methocel® K4MPRCR e 30 por cento de Ethocel® N10STD obtidas por compressão direta apresentaram bom perfil de liberação de teofilina e a difusão foi o principal mecanismo envolvido na liberação.

Development and in vitro evaluation of extended-release theophylline matrix capsules

Polymers like cellulose (MethocelTM K100MPRCR, K15MPRCR and E4MCR) at different proportions (15-35 percent) were used to slow the release of theophylline (100 mg) from capsules. Volumetric method for powder filling capsules was used to prepare the capsules. Drug release from capsules was performed using apparatus 1, at 100 rpm and 900 mL of intestinal medium without enzymes (pH 7.5), at 37 ºC, following the USP 28th ed. (Test 8). Dissolution profiles were compared to two batches of commercial extended-release capsules. Capsules compounded with 35 percent (wt/wt) of MethocelTM E4MCR showed dissolution profile according to the official especifications. Similar results were reproduced with other ten compounded batches. Commercial extended-release capsules containing theophylline pellets (100 mg) showed quick drug release when submitted to the same test, indicating that, in these conditions, the capsules did not show prolonged release. Mathematical models like zero-order, first-order and Higuchi were applied in kinetic studies of theophylline release from the compounded capsules. Polymers were efficient to control the release of theophylline in capsules involving diffusion and erosion as mechanisms, and that first-order model was the best fitted one for theophylline matrix capsules. These results support that compounded extended-release capsules can be prepared, since the drug release tests can be done.

Cápsulas de liberação modificada contendo 100 mg de teofilina foram preparadas com polímeros derivados da celulose (Methocel® K100MPRCR, K15MPRCR e E4MCR) em diferentes concentrações, 15-35 por cento, empregando-se o método volumétrico. Estudos de liberação do fármaco foram realizados de acordo com a Farmacopéia Americana 28 ed., (Teste 8), empregando aparato 1, rotação de 100 rpm e temperatura de 37 ºC em 900 mL de meio fluido intestinal sem enzimas (pH 7,5). Os perfis de dissolução foram comparados ao de duas especialidades farmacêuticas comerciais. A formulação, com 35 por cento de Methocel® E4MCR, evidenciou perfis de liberação de acordo com as especificações e os resultados foram reprodutíveis para 10 lotes manipulados com a mesma formulação. As cápsulas comerciais de liberação prolongada contendo 100 mg de teofilina (microgrânulos), submetidas ao mesmo ensaio, apresentaram rápida liberação do fármaco, indicando que a liberação não é fator limitante para a absorção. Avaliou-se a cinética de liberação do fármaco empregando os modelos matemáticos de ordem zero, primeira ordem e Higuchi. Conclui-se que as matrizes obtidas foram capazes de modular a liberação, envolvendo os mecanismos de difusão e erosão, prevalecendo o modelo de primeira ordem e que as cápsulas de liberação modificada podem ser manipuladas, desde que testes de liberação sejam realizados.

Formulation and in vitro evaluation of theophylline-Eudragit® sustained-release tablets

Tablets containing theophylline (66.67 porcento) based on a Eudragit® RS 30D and NE 30D matrices containing 10 porcento to 30 porcento of either of the polymer were produced by compression method. The influence of the different proportions of methacrylic esters, the use of lactose and tribasic calcium phosphate as diluents and also the effects of the addition of magnesium stearate as a hydrophobic agent lubricant on the theophylline release, were studied. Physicochemical analyses and drug content was evaluated. In vitro drug release studies were carried out in simulated gastric fluid without pepsin (pH1.2) and simulated intestinal fluid without pancreatin (pH7.5)...