Chitosan-decorated polystyrene-b-poly(acrylic acid) polymersomes as novel carriers for topical delivery of finasteride.

In view of the fact that the oral administration of finasteride (FIN) has resulted in various undesirable systemic side effects, the topical application of polystyrene and poly(acrylic acid)-based polymersomes (underexplored system) was investigated. Undecorated PS139-b-PAA17 and PS404-b-PAA63 vesicles (C3 and C7, respectively) or vesicles decorated with chitosan samples of different molecular weight (C3/CS-oligo, C7/CS-oligo, C3/CS-37 and C7/CS-37) were prepared by the co-solvent self-assembly method and characterized by small-angle X-ray scattering,transmission electron microscopy and dynamic light scattering techniques. In vitro release experiments and ex vivo permeation using Franz diffusion cells were carried out (through comparison with hydroethanolic finasteride solution). The ideal system should provide high finasteride retention in the dermis and epidermis while allowing some control of the drug release. The particle size and in vitro release were negatively correlated with the permeation coefficient and skin retention in both the epidermis and dermis. The findings that the longest lag time was obtained for the hydroethanolic drug solution and lowest permeation for the systems able to release the drug faster support the hypothesis that nanostructured systems may be required to enhance the penetration and permeation of the drug. Chitosan-decorated polymersomes interacted more strongly with the skin components than non-decorated samples, probably due to the positive surface charge, which increased the FIN retention and reduced the lag time. C7 polymersomes decorated with chitosan were more appropriate for topical applications (high retention in the dermis and epidermis and controlled drug delivery).

Nifedipine-loaded polymeric nanocapsules: validation of a stability-indicating HPLC method to evaluate the drug entrapment efficiency and in vitro release profiles.

A simple stability-indicating analytical method was developed and validated to quantify nifedipine in polymeric nanocapsule suspensions; an in vitro drug release study was then carried out. The analysis was performed using an RP C18 column, UV-Vis detection at 262 nm, and methanol-water (70 + 30, v/v) mobile phase at a flow rate of 1.2 mL/min. The method was validated in terms of specificity, linearity and range, LOQ, accuracy, precision, and robustness. The results obtained were within the acceptable ranges. The nanocapsules, made of poly(epsilon-caprolactone), were prepared by the solvent displacement technique and showed high entrapment efficiency. The entrapment efficiency was 97.6 and 98.2% for the nifedipine-loaded polymeric nanocapsules prepared from polyvinyl alcohol (PVA) and Pluronic F68 (PF68), respectively. The particle size and zeta potential of nanocapsules were found to be influenced by the nature of the stabilizer used. The mean diameter and zeta potential for nanocapsules with PVA and PF68 were 290.9 and 179.9 nm, and -17.7 mV and -32.7 mV, respectively. The two formulations prepared showed a drug release of up to 70% over 4 days. This behavior indicates the viability of this drug delivery system for use as a controlled-release system.

Estabilidade físico-química de formulações para nutrição parenteral neonatal manipuladas em hospital universitário / Physical and chemical stability of formulations for parenteral nutrition compounded at a university hospital

A estabilidade físico-química de três formulações para nutrição parenteral neonatal com diferentes quantidades de cátions bivalentes e de emulsão lipídica foi avaliada. As formulações foram analisadas nos tempos: 0, 24 e 48 horas, em três condições de temperatura diferentes de armazenamento: 2ºC-8ºC, 25ºC e 37ºC, mediante os seguintes parâmetros: pH, potencial zeta, tamanho e distribuição de partículas, microscopia óptica, propriedades reológicas, osmolaridade e aspecto visual. Os valores de pH mantiveram-se em todas as condições de estudo, em torno de 6,00 e os resultados de potencial zeta, em média, mostraram valores de - 27,65 mV. O tamanho das gotículas lipídicas apresentou-se constante e estável, em escala nanométrica, com gotículas não superiores a 5 μm em diâmetro. Os valores de viscosidade mantiveram-se constantes e os índices de fluxo apresentaram-se todos acima e próximos de 1,00. As osmolaridades teóricas apresentaram, em média, 822 mOsmol/L, todas inferiores ao limite máximo recomendado. Os sistemas emulsionados permaneceram visualmente estáveis e não foram notadas alterações de coloração, tampouco foram evidenciados processos de separação de fases nas formulações. Pode-se afirmar que as formulações apresentaram-se estáveis nas condições avaliadas. Demonstrou-se a necessidade e a importância da adoção de procedimentos de avaliação físico-química, somando-se ao controle microbiológico das formulações parenterais, para a garantia da eficácia da terapia e, principalmente, da segurança dessas formulações para os recém-nascidos.

The physical and chemical stability of three formulations for neonatal parental nutrition, made up with different amounts of divalent cations and lipid emulsion, were assessed. The formulations were analyzed at 0, 24 and 48 hours, under three different conditions of storage temperature: 2–8º C, 25º C and 37o C, in terms of the following parameters: pH, zeta potential, size and distribution of particles, optical microscopy, rheological properties, osmolarity and visual appearance. The pH remained, under all conditions studied, around 6.00 and the zeta potential was - 27.65 mV on average. The lipid droplet size was constant and stable, in the nanometer range, and no droplets exceeded 5 μm in diameter. The viscosities remained constant and all the flow behavior indices were above and close to 1.00. The theoretical osmolarities were, on average, 822 mOsmol/L, all below the recommended maximum value. The emulsion systems remained stable and there was no visually noticeable color change or evident phase separation in the formulations. It can be reported that all the formulations were stable under the conditions studied. The need and importance of adopting physicochemical evaluation procedures, in addition to the microbiological control of parental formulations, in order to guarantee the effectiveness of therapy, and especially the safety of these formulations for newborns, was demonstrated in this study.

Physicochemical and microbiological stability studies of extemporaneous antihypertensive pediatric suspensions for hospital use.

Extemporaneous suspensions of the antihypertensive agents furosemide, spironolactone and hydrochlorothiazide for pediatric use have been prepared at University Hospital (Federal University of Santa Catarina - Brazil). The aim of this work was to investigate the physicochemical and microbiological stability of these suspensions over the estimated shelf-life period of seven days and, if necessary, to optimize the formulations by improving the chemical stability. The pediatric suspensions were prepared using drug raw material and were stored at 25 ± 2°C and 5 ± 3°C. Chemical stability was evaluated by HPLC assay of the suspensions for drug content. Physical stability was evaluated by sedimentation volume, redispersibility, particle size, and zeta potential. Viable bacterial and fungal contaminations were assessed according to the official compendium. Furosemide and spironolactone suspensions as prepared herein can be stored for 7 days. However, the hydrochlorothiazide suspension formulation at pH 6.5 demonstrated poor chemical stability and was optimized by adjusting the pH to 3.3 where the drug exhibited acceptable stability. The optimized formulation demonstrated to be stable over the required period of 7 days.

Development and validation of an RP-HPLC method to quantitate acyclovir in cross-linked chitosan microspheres produced by spray drying.

An accurate, simple, reproducible, and sensitive liquid chromatographic method is developed and validated to quantitate acyclovir (ACV) in cross-linked chitosan microspheres produced by spray drying. The analysis is carried out using a reversed-phase C18 column with UV-vis detection at 254 nm. The mobile phase is diluted with pure water and acetonitrile (95:5 v/v) at a flow-rate of 0.8 mL/min. The parameters used in the validation process are: linearity, range, quantitation limit, detection limit, accuracy, specificity precision, and ruggedness. The retention time of acyclovir is approximately 3.5 min with symmetrical peaks. The linearity in the range of 1-10 microg/mL presents a correlation coefficient of 0.9999. The chitosan and the tripolyphosphate in the formulation do not interfere with the analysis, and the recovery is quantitative. Results are satisfactory, and the method proves to be suitable to quantitate ACV in cross-linked chitosan microspheres.

Desenvolvimento e validação de um método analítico para quantificação por espectroscopia UV de captopril em comprimidos de liberação prolongada / Development and validation of an UV analytic method intended for quantification of captopril in delayed release tablets

Um método analítico utilizando espectroscopia no ultravioleta (UV) foi desenvolvido e validado para quantificar o fármaco captopril em comprimidos de liberação prolongada. Os parâmetros utilizados no processo de validação foram: especificidade, linearidade e intervalo, precisão, exatidão e robustez. A linearidade no intervalo de 5.0 – 40.0 µg/mL apresentou um coeficiente de correlação de 0, 9998. Os excipientes das formulações não interferiram com a análise e a recuperação da amostra foi de 100, 20 ± 0,28 porciento. Todos os resultados foram satisfatórios e o método provou ser adequado para quantificar o captopril nos comprimidos de liberação prolongada