Characterization of matrix embedded formulations for combination spray-dried particles comprising pyrazinamide and rifampicin

Abstract

Dry powder inhalers (DPIs) are becoming increasingly popular in the treatment of both systemic and pulmonary diseases. In an effort to enhance the DPIs, we developed spray-dried particles (SDP) using highly branched cyclic dextrin (HBCD) as an excipient. Pyrazinamide (PZA) and rifampicin (RFP) were employed in the present study. The cytotoxicity of HBCD for an excipient of inhalable formulations was evaluated using A549 cell lines as a model of alveoli cells. No cytotoxic effect was observed. Moreover, unlike the formulation prepared with PZA only, combination SDPs achieved a fair fine particle fraction of both model drugs, especially the formulation prepared with 40% ethanol concentration ratio which obtained fine particle fraction (FPF) of 48.7% ± 6.9% and 51.2% ± 6.5% of PZA and RFP, respectively. The dissolution profile of the hydrophobic model drug, RFP was highly enhanced after being included in composite spray-dried powders. In a 60 min dissolution test, untreated hydrophobic RFP can only obtain a dissolution percentage of 9.7% ± 2.5%, while a dissolution percentage near 100% was obtained when it had been prepared into composite powder form, the improvement may be contributed by the acquired amorphous characteristics which were revealed in PXRD analysis. The deeper understanding on HBCD that was acquired through this study shows a great potential of HBCD to be applied as an additive in preparing DPIs.