The effect of spray drying solvent on in vitro deposition profiles and pulmonary absorption of rifampicin microparticles

Different solvents, dichloromethane (DCM) and water (W) were used as vehicles for the production of rifampicin microparticles using the spray drying technique. Two samples were prepared from aqueous solutions by dissolving the commercial rifampicin (CR) in water and being spray dried at 100°C (W100) and 150°C (W150). Another sample was prepared from dichloromethane solution by dissolving CR in water and being spray dried at 50°C (DCM50). The physical characteristics of the spray dried samples were examined by laser diffraction, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), helium densitometer, infrared spectroscopy (IR) and X-ray diffraction. The aerosolization performance of the samples was investigated using an Andersen cascade impactor. Pulmonary absorptions from different formulations were examined by an in situ pulmonary absorption experiment. The plasma concentration time profiles of rifampicin were prepared over 8 h following the intravenous and intrapulmonary administrations. Pharmacokinetics parameters such as half life (t1/2), mean residence time, AUC, Cmax and Tmax were determined for different formulations. In the pharmacokinetics analysis, the Tmax values for the samples spray dried from water significantly decreased. The Tmax values for the samples spray dried from dichloromethane and water were 60 and 30 min, respectively. The type of solvent used in the spray drying of rifampicin has influenced physical properties, in vitro deposition profiles and pharmacokinetic parameters of the drug.