The Study On Aqueous Aerosols Of Salbutamol Sulfate And Beclomethasone Dipropionate

Aqueous aerosol (AA) has been investigated and been used as target of our research. It also provides a new way to solve the problem of the prohibition of chlorofluorocarbon (CFC) used in aerosol.The aqueous drug solution was atomized using a metered jet nebulizer and ultrasonic AA to be inhaled via nose or mouth by animals. The water soluble salbutamol sulfate (SBT) and levofloxacin hydrochloride (LOF) and insoluble beclomethasone dipropionate (BDP) were used as the models. The SBT and LOF solution, BDP micro-emulsion and BDP ethanol(?)solution were used in the study. The laboratory investigations were carried out by nasal inhalation by rats and oral inhalation by Beagle dogs in comparison with the CFC metered-dose inhaler(MDI) and dry powder inhaler(DPI).The HPLC methods with fluorescence detection for determination of the concentration of SBT or LOF in lung of rats were established. The methods are sensitive with the LOQ of 0.10 μg/ml and 0.05μg/ml, respectively. The LC-MS/MS methods for determining the concentration of SBT in rat plasma and in Beagle dog plasma were established using terbutaline as internal standard with LOQ of 0.10 ng/ml and 0.05ng/ml, respectively. The LC-MS/MS method for determining the concentration of 17- beclomethasone monopropionate(17-BMP) in Beagle dog plasma were established for BDP pharmacokinetics test using BDP as the reference. The LOQ is 0.10 ng/ml.The apparatus were designed and made for nasal inhalation and oral inhalation. The later apparatus has not been reported yet in literature. The ultrasonic AAs were made for research.Both time-of-flight aerodynamic particle size analyzer (TOF method) and multiple-stage liquid impinger (MLI method) were used to evaluate particle size generated from ultrasonic AA to give the similar result of the average particle size of about 10 μm. The most particles produced from metered jet nebulizer, measured by laser diffraction method(LD method), were about 50μm, and some below 10 μm, and when the TOF method was used, some less than 20μm.By inhalation of the aerosols generated from SBT MDI and from ultrasonic AA of LOF solution, the amount of drug deposited in the lung of rats accorded with the Weibull equation. The equations in the experiments were:LnLn[100/(100-M_lung)]= 1.622Ln t-5.525andLnLn[100/(100-M_lung)] = -4.531 + 1.146 Ln t, respectively.The pharmacokinetic parameters in rats after nasal inhalation of SBT MDI were T_5min 33.38...