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Glucocorticoids are widely used for the treatment of eye inflammation followed or not by infection. Although effective, this class of drugs has significant adverse effects such as increased intraocular pressure and cataracts. Thus, the development of an innovative drug with greater efficacy and safety for the treatment of ophthalmic inflammation is of fundamental importance. The glucocorticoid derivative synthesized by molecular hybridization of phthalimide associated with budesonide revealed anti-inflammatory activity. Furthermore, this drug candidate was designed to eliminate the undesirable adverse effects of glucocorticoids. However, this compound has low water solubility, limiting its bioavailability for ocular use. In this sense, drug nanocrystals allow overcome this challenge by reducing the radius of the particles with a consequent increase in the surface area. This high increase in the ratio between the area and the volume of the particle allows the increase in the saturation solubility and mucoadhesiveness of the drug candidate. Moreover, the development of pharmaceutical products must be carried out using a systematic approach that allows revealing interactions or effects between components of the formula and the critical process parameters. Thus, in the present study, design of experiment (DoE) was used to develop nanosuspension of this glucocorticoid derivative. The reduction in the particle size of the drug candidate was carried out by applying super small scale wet bead milling, giving rise to particles with an average size equal to 165.0 nm. The application of the statistical tool allowed formula optimization. The parameters that influence the particle size reduction were determined: stirring speed and the surfactant concentration. Besides, the statistical approach revealed the interaction between the types of surfactants (synergistic stabilizing action). Among the surfactants tested, those that promoted the greatest reduction in particle size were cationic: benzalkonium chloride (BAK) or cetylpyridinium chloride (CPC). These usually do not perform this function in conventional ophthalmic preparations. In general, they are used as antimicrobial preservatives in multi-dose preparations. The optimized formulation presented the following composition: 1.0 % (w/w) of glucocorticoid derivative and 0.092 % (w/w) of cetylpyridinium chloride. This nanosuspension was evaluated for its morphology, physicochemical characteristics, and in vitro mucoadhesiveness test. Therefore, the present study allowed the development of an innovative product with potential applications in the treatment of eye inflammations. Glicocorticoides são amplamente utilizados para o tratamento de inflamações oculares seguidas ou não de infecção. Embora eficazes, essa classe de fármacos apresenta efeitos adversos significativos como aumento da pressão intraocular e catarata. Assim, o desenvolvimento de medicamento inovador com maior eficácia e segurança para o tratamento de inflamações oftálmicas é de fundamental importância. O derivado glicocorticoide sintetizado por hibridação molecular da ftalimida associada a budesonida revelou atividade anti-inflamatória. Além disso, esse candidato a fármaco foi planejado visando eliminar os indesejáveis efeitos adversos dos glicocorticoides. Entretanto, esse composto apresenta baixa solubilidade em água limitando sua biodisponibilidade para o uso ocular. Nesse sentido, os nanocristais de fármacos permitem superar tal desafio por meio da redução do raio das partículas com consequente aumento da área de sua superfície. Esse elevado aumento da razão entre a área e o volume da partícula permite o aumento da solubilidade de saturação e da mucoadesividade do candidato a fármaco. Adicionalmente, o desenvolvimento de produto farmacêutico deve ser realizado empregando abordagem sistemática que permita revelar interações ou efeitos entre os componentes da fórmula e os parâmetros críticos de processo. Assim, no presente estudo, foi utilizado planejamento de experimentos (DoE) para o desenvolvimento de nanosuspensão do derivado glicocorticoide. A redução do tamanho de partícula do candidato a fármaco foi efetuada por meio de moagem via úmida em escala reduzida originando partículas de tamanho médio igual a 165,0 nm. A aplicação da ferramenta estatística permitiu a otimização da fórmula. Foram determinados os parâmetros que influenciaram na redução do tamanho das partículas: a velocidade de agitação e a concentração de tensoativo. Além disso, a abordagem estatística permitiu revelar a interação entre os tipos de tensoativos (ação sinérgica de estabilização). Dentre os tensoativos testados, aqueles que promoveram a maior redução do tamanho de partícula foram os catiônicos: cloreto de benzalcônio (BAK) ou cloreto de cetilpiridínio (CPC). Esses usualmente não exercem essa função nas preparações oftálmicas convencionais. Em geral são utilizados como conservantes em preparações multidoses. A formulação otimizada apresentou a seguinte composição: 1,0% (m/m) do composto híbrido derivado glicocorticoide e 0,092% (m/m) de cloreto de cetilpiridínio. Essa nanosuspensão foi avaliada quanto sua morfologia, características físico-químicas e teste in vitro de mucoadesividade. Assim sendo, o presente estudo permitiu o desenvolvimento de produto inovador com potencial aplicação no tratamento de inflamações oculares.

Unprotected chronic exposure to ultraviolet radiation generates many harmful effects to human skin and UV filters are essential to health, however, traditional sunscreens do not provide enough protection against cutaneous oxidative stress, a process amplified by UV radiation. Therefore, is been proposed the development of multifunctional photoprotective formulations, acting in the absorption/reflection of UV radiation and assisting in cutaneous homeostasis. In the present study, ferulic acid is used in conjunction with two sunscreens, bemotrizinol and ethylhexyl triazone, for the determination of biosafety and efficacy methods, using techniques that better elucidate the effects of ferulic acid. Skin permeation assays were performed by applying a formulation containing the three substances in the stratum corneum of volunteers, which were removed by the tape stripping method (ex vivo) with follow quantification by high performance liquid chromatography (HPLC). The test was able to evaluate the penetration depth of the substances, characterizing them. In addition, the simultaneous quantification of the three substances was performed by a single and fast method, facilitating their analysis and improving the technique. Also, TBARS (thiobarbituric acid reactive substances) assays were performed in stratum corneum removed by tape stripping (ex vivo), evaluating the potential of cutaneous lipid peroxidation, with or without ferulic acid. To date, it is the first time that TBARS method is used to characterize the stratum corneum (ex vivo) and quantified by HPLC. The protocol developed may aid in the efficacy of antioxidant agents in studies aimed at elucidating the level of lipid peroxidation caused by drugs and cosmetics, and even in carrying out baseline studies characterizing different ethnicities and genders. As last, an anti-inflammatory in vivo assay with Laser Doppler flowmetry equipment was used to compare the sunscreen formulation with or without ferulic acid. Data indicated that the antioxidant reduced the angular coefficient of the perfusion units, mitigating the inflammatory effects. Furthermore, a significant difference was found between the genders, suggesting a more pronounced inflammatory reaction in women. Ferulic acid proved to be a valuable resource, besides being safe and raise the SPF of sunscreens, it also mitigates the effects of inflammation. Unprotected chronic exposure to ultraviolet radiation generates many harmful effects to human skin and UV filters are essential to health, however, traditional sunscreens do not provide enough protection against cutaneous oxidative stress, a process amplified by UV radiation. Therefore, is been proposed the development of multifunctional photoprotective formulations, acting in the absorption/reflection of UV radiation and assisting in cutaneous homeostasis. In the present study, ferulic acid is used in conjunction with two sunscreens, bemotrizinol and ethylhexyl triazone, for the determination of biosafety and efficacy methods, using techniques that better elucidate the effects of ferulic acid. Skin permeation assays were performed by applying a formulation containing the three substances in the stratum corneum of volunteers, which were removed by the tape stripping method (ex vivo) with follow quantification by high performance liquid chromatography (HPLC). The test was able to evaluate the penetration depth of the substances, characterizing them. In addition, the simultaneous quantification of the three substances was performed by a single and fast method, facilitating their analysis and improving the technique. Also, TBARS (thiobarbituric acid reactive substances) assays were performed in stratum corneum removed by tape stripping (ex vivo), evaluating the potential of cutaneous lipid peroxidation, with or without ferulic acid. To date, it is the first time that TBARS method is used to characterize the stratum corneum (ex vivo) and quantified by HPLC. The protocol developed may aid in the efficacy of antioxidant agents in studies aimed at elucidating the level of lipid peroxidation caused by drugs and cosmetics, and even in carrying out baseline studies characterizing different ethnicities and genders. As last, an anti-inflammatory in vivo assay with Laser Doppler flowmetry equipment was used to compare the sunscreen formulation with or without ferulic acid. Data indicated that the antioxidant reduced the angular coefficient of the perfusion units, mitigating the inflammatory effects. Furthermore, a significant difference was found between the genders, suggesting a more pronounced inflammatory reaction in women. Ferulic acid proved to be a valuable resource, besides being safe and raise the SPF of sunscreens, it also mitigates the effects of inflammation.