Dexamethasone Acetate Nanocrystals, Characterization and Dissolution Studies in Presence of Polymorphic Phases.

BACKGROUND: A drug with poor water-solubility, like Dexamethasone acetate, can present lower bioavailability conventional for pharmaceutical formulations, and the presence of polymorphs in the raw material can lead to drug quality problems. OBJECTIVE: In this study, nanocrystals of dexamethasone acetate were synthesized by high pressure homogenizer (HPH) method in surfactant poloxamer 188 (P188) solid dispersion and the bioavailable in raw material with polymorphism presence was evaluated. METHODS: The powder pre-suspension was prepared by the HPH process, and the nanoparticles formed were incorporated in P188 solutions. The nanocrystals formed were characterized by techniques of XRD, SEM, FTIR, thermal analysis by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA), dynamic light scattering (DLS) to analyze the particle size and zeta potential, and in vitro evaluation by dissolution studies. RESULTS: The characterization techniques were adequate to show the presence of raw material with physical moisture between two dexamethasone acetate polymorphs. The nanocrystals formed in the presence of the P188 in the formulation showed a considerable increase in the rate of dissolution of the drug in the medium and in the size of the stable nanocrystals, even in the presence of dexamethasone acetate polymorphs. CONCLUSION: The results showed that it was possible to produce dexamethasone nanocrystals by HPH process with regular size by the presence of the small amount of P188 surfactant. This article presents a novelty in the development of dexamethasone nanoparticles that have different polymorphic forms in their physical composition.

Zinc-Based Nanoparticles Reduce Bacterial Biofilm Formation.

Biofilm formation is important for microbial survival in hostile environments and a phenotype that provides microorganisms with antimicrobial resistance. Zinc oxide (ZnO) and Zinc sulfide (ZnS) nanoparticles (NPs) present potential antimicrobial properties for biomedical and food industry applications. Here, we aimed to analyze, for the first time, the bactericidal and antibiofilm activity of ZnS NPs against Staphylococcus aureus, Klebsiella oxytoca, and Pseudomonas aeruginosa, all medically important bacteria in developed countries. We compared ZnS NPs antimicrobial activity to ZnO NPs, which have been extensively studied. Using the colorimetric XTT reduction assay to observe the metabolic activity of bacterial cells and the crystal violet assay to measure biofilm mass, we demonstrated that ZnS and ZnO had similar efficacy in killing planktonic bacterial cells and reducing biofilm formation, with S. aureus being more susceptible to both therapeutics than K. oxytoca and P. aeruginosa. Crystal violet staining and confocal microscopy validated that Zn NPs inhibit biofilm formation and cause architectural damage. Our findings provide proof of principle that ZnS NPs have antibiofilm activity, and can be potentially used in medical and food industry applications, such as treatment of wound infections or package coating for food preservation. IMPORTANCE Zinc (Zn)-based nanoparticles (NPs) can be potentially used in medical and food preservation applications. As proof of principle, we investigated the bactericidal and antibiofilm activity of zinc oxide (ZnO) and zinc sulfide (ZnS) NPs against medically important bacteria. Zn-based NPs were similarly effective in killing planktonic and biofilm-associated Staphylococcus aureus, Klebsiella oxytoca, and Pseudomonas aeruginosa cells. However, S. aureus was more susceptible to these investigational therapeutics. Although further studies are warranted, our findings suggest the possibility of future use of Zn-based NPs in the treatment of skin infections or preservation of food.

Solid-State Characterization of Spironolactone 1/3 Hydrate.

Spironolactone (SPR) is a poorly water-soluble drug widely used for the treatment of various diseases. The objective of this study was to carry out the preparation and solid-state characterization of SPR 1/3 hydrate. The solid form was generated by an unreported recrystallization process in acetone and characterized for the first time by a combination of X-ray powder diffraction (XRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), Fourier-transform infrared spectroscopy (FTIR), equilibrium solubility, and an accelerated stability study. XRD, DSC, and TGA studies revealed that SPR 1/3 hydrated converts completely to form II after heating to 180°C. Solubility studies at 37°C showed that SPR 1/3 hydrate was statistically less soluble than SPR form II in all tested media and that SPR form II partially converts to SPR 1/3 hydrate in aqueous media. Accelerated stability studies demonstrated that both forms were physically and chemically stable up to 6 months (40°C/75% RH). We concluded that contamination of SPR 1/3 hydrate in SPR raw materials is undesirable. Taking this into account we recommend its polymorphic monitoring either in active pharmaceutical ingredients or commercial tablets by solid-state identification/quantification methods (XRD, DSC, TGA, and FTIR). Of these, XRD proved to be the most conclusive and accurate.