ABSTRACT
The aim of this study was to evaluate the effect of solvents used in the spray drying and the aerodynamic properties of the rifampicin microparticles and pulmonary absorption of the microparticles. Different mixtures of dichloromethane and water were used as solvents for spray drying of rifampicin microparticles. The water to dichloromethane ratios were 25:75, 50:50, 75:25, 80:20, 90: 10 and 100:0. The solutions were dried at inlet temperature of 70 °C. The powder properties of the samples were examined by laser diffraction, scanning electron microscopy [SEM], helium densitometer and infrared spectroscopy [IR]. The aerosolization performance of these formulations was investigated using an Andersen cascade impactor. Pulmonary absorptions of formulations were examined by the in situ pulmonary absorption described by Enna and Schanker method. The plasma concentration time profiles of rifampicin were constructed 8 hours following the intravenous and the intrapulmonary administrations. The pharmacokinetics parameters, C[max], T[max], t[1/2] AUC, mean residence time [MRT], K[a] and K[e] were determined for each formulations. The T[max] values for the samples decreased by increase in the amount of water in the initial feed. The T[max] values for the spray dried samples from the different mixtures of dichloromethane and water were 60 [min] and 30 [min] respectively. The solvent mixture as the spray drying vehicle played an important role in the in vitro and in vivo lung deposition. The type of spray drying vehicle showed significant effect on the aerodynamic behavior and pharmacokinetic parameters of the particles. The pulmonary absorption of drug revealed the possibility of achieving the minimal inhibitory concentration [MIC] of the antibiotics. The spray drying vehicle only affected absorption patterns of the formulations and it did not have any effect on the elimination rat of particle
Subject(s)
Animals, Laboratory , Rifampin/chemical synthesis , Rifampin/pharmacokinetics , Solvents/pharmacokinetics , Absorption , Lyases , Water , Microscopy, Electron, Scanning , Spectroscopy, Near-Infrared , Densitometry , Rats, WistarABSTRACT
La inhalación de disolventes industriales es uno de los problemas de salud más importantes tanto en medicina del trabajo, como en la esfera de la farmacodependencia cuando estas substancias son inhaladas involuntaria o voluntariamente. La inhalación voluntaria ha crecido alarmantemente en las ultimas décadas, convirtiendola en un objeto de estudio de importancia primaria, tanto por sus orígenes como por su magnitud. Los estudios pioneros de Costero y Barriso entre otros dan una idea de la magnitud de algunos de los efectos, que tiene esta farmacodependencia. Este trabajo se enfoca al estudio del efecto de la inhalación de tíner por periodos prolongados tienen sobre la morfología y la función del hígaso de la rata y la fracción mitocondrial aislada de ese órgano.