25In the present study, in vitro permeation experiments in a Franz diffusion cell were performed 26 using different synthetic polymeric membranes and pig ear skin to evaluate a rivastigmine

The purpose of this study was to prepare engineered particles of rivastigmine hydrogen tartrate (RHT) and to characterize the physicochemical and aerodynamic properties, in comparison to a lactose carrier formulation (LCF). Microparticles were prepared from ethanol/water solutions containing RHT with and without the incorporation of L-leucine (Leu), using a spray dryer. Dry powder inhaler formulations prepared were characterized by scanning electron microscopy, powder X-ray diffraction, laser diffraction particle sizing, ATR-FTIR, differential scanning calorimetry, bulk and tapped density, dynamic vapour sorption and in vitro aerosol deposition behaviour using a next generation impactor. The smooth-surfaced spherical morphology of the spray dried microparticles was altered by adding Leu, resulting in particles becoming increasingly wrinkled with increasing Leu. Powders presented low densities. The glass transition temperature was sufficiently high (>90 °C) to suggest good stability at room temperature. As Leu content increased, spray dried powders presented lower residual solvent content, lower particle size, higher fine particle fraction (FPF<5 μm), and lower mass median aerodynamic diameter (MMAD). The LCF showed a lower FPF and higher MMAD, relative to the spray dried formulations containing more than 10% Leu. Spray dried RHT powders presented better aerodynamic properties, constituting a potential drug delivery system for oral inhalation.

Abstract. The intramuscular administration of the injectable suspension betamethasone sodium phosphate (BSP) and betamethasone dipropionate (BD) has immediate therapeutic activity due to solubilized BSP and prolonged activity resulting from the slow release of BD micro-crystals. The purpose of this study was to develop and validate a dissolution method for BD in intramuscular injectable suspensions with detection by high-performance liquid chromatography (HPLC) method. Five commercial products presented a distribution of particle sizes, ranging between 7.43 and 40.25 μm as measured by laser diffraction. It was also found that particle sizes differed between batches of the same product. The different products were tested using the paddle apparatus, with stirring speeds of 25 and 50 rpm in 300 mL of phosphate buffer; simulated body fluid, muscle fluid, and synovial fluid were used as biorelevant dissolution media at 37±0.5°C. It was verified that not only does average particle size affect the dissolution rate, but also the mode and the polydispersity index of the particles. Discriminatory power was obtained using the in vitro dissolution method with 0.1 M sodium phosphate buffer pH 7.4 containing 0.1% sodium lauryl sulfate and a stirring speed of 50 rpm. The HPLC-method is linear, precise, selective, and accurate for the quantification of BSP and BD in dissolution profile testing. This dissolution method can be utilized as a method to control the quality of these injectable suspensions.KEY WORDS: dipropionate betamethasone; dissolution test; intramuscular injectable suspensions; simulated muscular fluid; sodium phosphate betamethasone.

In this study, we report the synthesis of twenty new acridine–thiosemicarbazone derivatives and their antiproliferative activities. Mechanisms of action such as the inhibition of topoisomerase IIα and the interaction with DNA have been studied for some of the most active derivatives by means of both in silico and in vitro methods, and evaluations of the non-clinical toxicities (in vivo) in mice. In general, the compounds showed greater cytotoxicity against B16-F10 cells, with the highest potency for DL-08 (IC50 = 14.79 µM). Derivatives DL-01 (77%), DL-07 (74%) and DL-08 (79%) showed interesting inhibition of topoisomerase IIα when compared to amsacrine, at 100 µM. In silico studies proposed the way of bonding of these compounds and a possible stereoelectronic reason for the absence of enzymatic activity for CL-07 and DL-06. Interactions with DNA presented different spectroscopic effects and indicate that the compound CL-07 has higher affinity for DNA (Kb = 4.75 × 104 M−1; Ksv = 2.6 × 103 M−1). In addition, compounds selected for non-clinical toxicity testing did not show serious signs of toxicity at the dose of 2000 mg/kg in mice; cytotoxic tests performed on leukemic cells (K-562) and its resistant form (K-562 Lucena 1) identified moderate potency for DL-01 and DL-08, with IC50 between 11.45 and 17.32 µM.

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Background: Topical administration of dapsone can be an alternative route for treatment of leprosy and can also provide new therapeutic applications for an established drug. However, the physicochemical properties of dapsone make it difficult to incorporate into conventional formulations. The current study was directed toward developing a stable nanoemulsion that contains dapsone which can be adapted for topical use. Methods: Nanoemulsions were prepared using isopropyl myristate or n-methyl-pyrrolidone as the oil phase, and characterized according to their mean droplet size, conductivity, refractive index, pH, drug content, and stability. The in vitro release of dapsone and its ability to permeate the epidermis were also evaluated. Results: Physicochemical characterization demonstrated that nanosystems were formed, which had a uniform droplet distribution and a pH compatible with the skin surface. Use of n-methyl-pyrrolidone provided a greater nanoemulsion region and higher solubilization of dapsone, and increased the in vitro release rate when compared with a nanoemulsion prepared using isopropyl myristate. However, use of isopropyl myristate promoted an increase in in vitro epidermal permeation that followed the Higuchi model. This demonstrates the ability of a nanosystem to influence permeation of dapsone through the skin barrier. Furthermore, the nanoemulsions developed and evaluated here had ideal physicochemical stability over a 3-month period. Conclusion: Incorporation of dapsone into a nanoemulsion may be a promising system for enabling topical delivery of dapsone, while minimizing skin permeation, for the treatment of acne. The method developed here used isopropyl myristate as the oil phase, and promoted permeation of dapsone through the skin barrier for the treatment of leprosy upon use of n-methylpyrrolidone as the oil phase.

Bacterial infections represent one of the leading causes of mortality in the world. Among causative pathogens, S. aureus is prominently known as the underlying cause of many multidrug resistant infections that are often treated with the first-line choice antibiotic vancomycin (VCM). Loading antibiotics into polymeric nanoparticles (Np) displays promise as an alternative method to deliver therapy due to the greater access and accumulation of the antibiotic at the site of the infection as well as reducing toxicity, irritation and degradation. The aim of this work was to prepare, characterize and evaluate VCM-loaded nanoparticles (VNp) for use against S. aureus strains. Moreover, conjugation of Nps with holo-transferrin (h-Tf) was investigated as an approach for improving targeted drug delivery. VNp were prepared by double emulsion solvent evaporation method using PLGA and PVA or DMAB as surfactants. The particles were characterized for size distribution, Zeta Potential, morphology by transmission electron microscopy, encapsulation yield and protein conjugation efficiency. Process yield and drug loading were also investigated along with an in vitro evaluation of VNp antimicrobial effects against S. aureus strains. Results showed that Np were spontaneously formed with a mean diameter lower than 300 nm in a narrow size distribution that presented a spherical shape. The bioconjugation with h-Tf did not appear to increase the antimicrobial effect of VNp. However, non-bioconjugated Np presented a minimal inhibitory concentration lower than free VCM against a MRSA (Methicillin-resistant S. aureus) strain, and slightly higher against a 6 Author to whom any correspondence should be addressed.

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