RESUMEN
The purpose of this research was to determine the effect of major compositional changes on the bioavailability of piroxicam from immediate-release formulations filled in hard gelatin capsules. The capsules were manufactured according to a 2(5-1) + star point (resolution V) experimental design to investigate the effects of sodium lauryl sulfate level, magnesium stearate level, lactose/microcrystalline cellulose ratio, piroxicam particle size, and lubricant blending time. Sodium lauryl sulfate level, lactose level, and piroxicam particle size were the most important main effects affecting dissolution. Lubricant level and lubricant blending time were either not significant (5% level) or were among the lowest ranking of factors affecting dissolution in standardized pareto analysis. Three of these formulations exhibiting slow, medium, and fast dissolution were compared to a single lot of the Innovator (commercial) product in a small bioavailability study. The slow formulation did not meet the USP dissolution specification for piroxicam capsules. Compositionally, the experimental formulations represented major changes in piroxicam particle size, level of filler, and level of sodium lauryl sulfate. Sixteen healthy volunteers received each formulation (20 mg) in a four-way crossover design. The three Maryland manufactured formulations were bioequivalent with the commercial product and were also bioequivalent among themselves. The major changes incorporated into these formulations did not result in major differences in bioavailability. The dissolution profiles which discriminated between the formulations in vitro did not accurately represent the in vivo bioavailability results. The results of this study are part of the research database that supports SUPAC-IR, an FDA guidance that provides relaxed testing and filing requirements for scale-up and post-approval changes to immediate-release oral solid dosage forms.
Asunto(s)
Antiinflamatorios no Esteroideos/administración & dosificación , Piroxicam/administración & dosificación , Adulto , Disponibilidad Biológica , Cápsulas , Química Farmacéutica , Femenino , Humanos , Masculino , Piroxicam/farmacocinética , Solubilidad , Equivalencia TerapéuticaRESUMEN
Cultures of Pseudomonas aeruginosa PAO grown under uninterrupted broad-spectrum light showed different pigmentation from dark-grown cultures. Whereas dark-grown bacteria produced pigments which resulted in blue-purple coloured agar, light-grown organisms produced red coloured plates. Extraction and quantification of pigments showed that both dark- and light-grown cultures produced similar concentrations of pyorubrin (red) and pyoverdin (yellow). In contrast, the concentration of pyocyanin (blue) was substantially reduced under certain lighting conditions. This decrease was dependent on both the light intensity and wavelength and occurred with light in the ultraviolet and violet region of the spectrum. After its release from bacteria, pyocyanin was rapidly and nonreversibly photoinactivated with first-order kinetics to produce colourless photoproduct(s).
Asunto(s)
Luz , Pigmentación/efectos de la radiación , Pseudomonas aeruginosa/efectos de la radiación , Pseudomonas aeruginosa/metabolismo , Piocianina/metabolismo , Piocianina/efectos de la radiaciónRESUMEN
The ability of three heterotricyclic dyes to photosensitize dermatophyte fungi was studied with Trichophyton mentagrophytes and Microsporum gypseum. In vitro studies showed that methylene blue, neutral red, and proflavine were capable of killing these fungi when used in conjunction with broad-spectrum light. Proflavine, however, killed both fungi most rapidly and was used for further studies. Fungal killing by proflavine plus light was dependent on dye concentration, pH, light wavelength, and light intensity. Based on the in vitro studies, a treatment regimen was developed for in vivo use on experimentally infected animals. When treatment of guinea pigs inoculated with T. mentagrophytes was begun during fungal invasion, lesion formation at inoculated sites was either prevented or substantially reduced. When treatment was begun after lesion formation, however, light-plus-dyed treated sites showed only slightly faster curing than untreated sites.