| Objective: To prepare dry powder inhalation with salbutamol sulfate(SS) and improve the efficiency of pulmonary drug delivery. We set a precedent about new Aztreonam(AZT) dry powder inhaler, and select amino acids as the excipients that fit for pulmonary delivery. At the same time, we carry out the research about the influence of amino acids for crystal.Methods:(1) The evaluation methods of SS and AZT dry powder inhalers(DPI) were as follow: the two drugs HPLC determination method, powder physicochemical properties, effectively deposition rate in vitro and the crystal of DPI.(2) Prepare SS powders by micro/nano-spray drying equipment, adding in lactose and leucine as excipients. The deposition rate in vitro was as the main evaluation index, then investigate the effects of leucine.(3) That’s the first time to prepare AZT dry powder inhaler with spray drying technique. So select 5 kinds of amino acids as excipients, and analysis the influence of amino acids on effective deposition rate and crystal of aztreonam spray-dried powders for pulmonary drug delivery.Results:(1) The HPLC determination method of SS and AZT was stable and reliable; which meet the standard of content determination.(2) With micro/nano spray drying, the drugs powders was prepared, optimized the process parameters, and keep the aerodynamic particle size within the range of 0.5 to 5μm.(3) The SS drug powders is not stable after micro/nano spray drying, but the stability of the powder is ameliorated by adding leucine, and the efficiency deposition in vitro obviously improved.(4) AZT was selected as model drug. The aerodynamic particle sizes of five kind amino acids powders except glycine were below 2 microns. Among them, effective deposition efficiency by adding leucine, histidine and lysine were increased by 16.3%, 5.96%, and 19.86% respectively. In addition, the amino acid can improve recrystallization phenomenon.(5)Screening the leucine concentration, the fine particle fraction(FPF) get to 62.40%, significantly improve the performance of the spray powders. Screening the histidine concentration, the deposition efficiency in vitro get to 59% after adding histidine.(6) The FPF of AZT nano-spray drying powder reaches to 41.23% after adding leucine, effective powder deposition efficiency up to 85.07%.Conclusion: In this paper, the spray drying process was used to prepare dry powder inhalers, and establish the evaluation method pulmonary drug delivery in vitro, the atomization performance SS and AZT was good. The physical and chemical properties and pulmonary delivery in vitro of powder deposition has been improved by adding amino acid. In addition, the powder particle morphology structure were affected. Comparing variable proportion, the AZT-LEU-60-40 was the most suitable formula. The research has laid a theoretical basis for the clinical development of AZT pulmonary drug delivery system. |
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