The effect of vehicles on spray drying of rifampicin inhalable microparticles: In vitro and in vivo evaluation

Abstract

Backgrond and the purpose of the study: 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.

Methods: 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.

Results and major conclusions: 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.