María José de Jesús Valle

Development and validation of an HPLC method for vancomycin and its application to a pharmacokinetic study.

A rapid and simple method of high performance liquid chromatography with UV detection for the quantification of vancomycin in artificial perfusion fluid and lung tissue samples has been developed and validated. Chromatographic separation was carried out in a Nucleosil 120 C(18) 5 microm column (length, 15 cm; inner diameter, 0.4 cm) using a mixture of 0.05 M NH(4)H(2)PO(4) (pH 4)-acetonitrile (92:8, v/v) as the mobile phase at a flow rate of 1 mL/min, with UV detection at 220 nm. The method used for the vancomycin quantification showed linearity for concentration ranges of 0.1-2, 2-15 and 15-250 microg/mL, with r(2)=0.9985, 0.9996 and 0.9985, respectively. The limit of quantification of the method was 0.1 microg/mL and the coefficients of variation of the between- and within-day precision showed values between 0.6% and 7.0%. The retention time of vancomycin was 8.5 min. The method was used successfully to study the pharmacokinetics of vancomycin in isolated rat lung after its administration through the systemic and inhalatory routes.

Pulmonary versus systemic delivery of antibiotics : Comparison of vancomycin dispositions in the isolated rat lung

ABSTRACT Vancomycin dispositions in the respiratory system were compared after systemic and inhalatory administration under two respiratory conditions using the isolated-lung model. Inhalatory delivery led to much higher drug levels in pulmonary tissue and fluids. The respiratory pattern affects vancomycin disposition in the pulmonary system regardless of the administration route.

Albumin micro/nanoparticles entrapping liposomes for itraconazole green formulation

Abstract Itraconazole‐loaded micro/nanoparticles containing albumin and liposomes were prepared by a technological process that avoids the use of organic solvents and crosslinker agents. The particles were characterized, lyophilized and formulated as tablets. Dynamic light scattering was used to determine the hydrodynamic diameter and zeta potential of the particles; optical and scanning‐electron microscopy was used to evaluate their morphology. Spherical shaped particles of different sizes and zeta potential were obtained. An exponential relationship between the zeta potential and the albumin/cationic lipid molar ratio was established. Drug entrapment efficiency values were in the range of 51–68%, with no statistical differences among albumin feeding concentrations. Mannitol was used as lyophilization additive and the freeze‐dried cake was directly compressed into tablets, suitable for vaginal administration. The results from the in vitro drug delivery assay show the influence of albumin on the itraconazole delivery profile; a rapid release was observed for particles with higher albumin amount compared to those with lower protein content. According to the results of this study, albumin particles entrapping liposomes prove to be a green pharmaceutical vehicle with a high potential for delivery of hydrophobic and highly albumin‐bound drugs. Graphical abstract Figure. No Caption available.

Lyophilized tablets for focal delivery of fluconazole and itraconazole through vaginal mucosa, rational design and in vitro evaluation

&NA; The present work deals with the rational design and in vitro evaluation of vaginal tablets for focal delivery of fluconazole (FLZ) and itraconazol (ITZ). Drug loaded liposomes with and without d‐alpha‐tocopheryl polyethylene glycol 1000 succinate (vit E TPGS) were prepared by direct sonication of the components and mixed with albumin to obtain albusomes. Tablets were obtained by direct compression of the lyophilized cake. The influence of vit E TPGS on size, zeta potential and entrapment efficiency (EE%) of liposomes and albusomes was evaluated. Tablet swelling and drug release were studied by in vitro assays. Vit E TPGS neither affected the zeta potential nor the EE% of liposomes and albusomes, but affected the liposomes size and the tablet disintegration time. A rapid erosion was observed for the tablets with the highest content of vitamin, while a slow swelling for those lacking the vitamin (swelling index = 57.76 ± 13.51%). A faster drug release profile was obtained for the former compared to the latter. The in vitro assay showed that FLZ diffused and solved in the vaginal fluid simulant while ITZ remained into the albusomes, which slowly released ITZ‐albumin complex and ITZ‐loaded liposomes, both suitable carriers for drug transport to deeper vaginal endothelium. Graphical abstract Figure. No caption available.