Pulmonary delivery of rifampicin microspheres using lower generation polyamidoamine dendrimers as a carrier

• Different generation polyamidoamine dendrimers were synthesized and characterized.
• PAMAM and rifampicin were co-spray dried to produce inhalable microspheric.
• G3 dendritic microspheres were identified as carriers for the pulmonary delivery.

Different generations (G1, G2 and G3) of polyamidoamine dendrimers (PAMAM) were synthesized and co-spray dried with rifampicin to produce inhalable microspheric particles for pulmonary delivery. The particle size distribution, morphology and density of the designed formulations were characterized by laser diffraction, scanning electron microscopy (SEM) and helium densitometer, respectively. The aerosolization performance of these formulations was investigated using an Andersen cascade impactor. The formulations were efficient aerosols having favorable fine particle fraction (FPF) and emitted fraction (EF), suggesting that the powders were suitable for inhalation. The absorptions of rifampicin following pulmonary administration of different formulations were also examined using an in situ pulmonary absorption method. The pharmacokinetic profiles of different rifampin formulations were studied following intrapulmonary administrations for 60 h. The pharmacokinetics parameters such as Cmax, tmax, t1/2, mean residence time (MRT) and the AUC were calculated separately. It was evident that the tmax value of the formulations was decreased while Cmax value was increased followed by PAMAM dendritic generations increased from G1 to G3. The lower generation PAMAM microspheres were found to have significant impact on the pharmacokinetics parameters of rifampicin and ultimately drug bioavailability. In this study, PAMAM G3 dendritic microsphere was identified as suitable drug carriers for the pulmonary delivery of rifampicin into lung tissues.

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