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

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

relation between molecular properties of drugs and their transport across the intestinal membrane

The aim of this study was to investigate the relationship between the intestinal absorption of structurally diverse model drugs across the rat intestinal mucosa and their molecular properties. Permeability coefficients for 13 compounds were determined in anaesthetized rats. Drug solution in phosphate buffered saline [PBS] was perfused through the intestinal segment with flow rate of 0.21 ml/min and samples were taken from outlet tubing at different time points up to 90 min. The permeability values ranged from 1.6 x [10-5] to 2 x [10-4] cm/sec for atenolol and ibuprofen respectively. Molecular properties of drugs including the number of hydrogen bond donors and acceptors, log P, logD, topological polar surface area and number of rotatable bonds were considered. The results indicated that compounds which meet 10 or fewer number of rotatable bonds and topological surface area equal to or less than 140 A° have a high probability of good intestinal permeability and fraction of dose which is absorbed in human. Moreover the results indicated that lower number of hydrogen bond counts and higher logD and logP values are associated with higher permeability and bioavailabilty of drugs. Therefore the experimental and computational methods could be used for the prediction of intestinal drug permeability