Pulmonary Administration Preparation Of Phospholipid Modified Nanocrystals

Pulmonary delivery is the best way to treat respiratory tract diseases.However,the inhaled drugs used in clinic are frequently administered and patients are poorly treated.Therefore,it is necessary to develop a lung sustained-release formulation.However,due to the absence of appropriate vectors and evaluation techniques,there is currently no mature formulation to achieve lung release.For the poor compatibility status of polymer material in lung,we chose the ciclesonide and budesonide,fluticasone propionate as model drug,to prepare micron grained and nanocrystalline formulation.The volatile oil of Houttuynia cordata Thunb with different particle size,solid lipid nanoparticles and nano crystal suspension were selected to compare the inhalable properties.In this paper,methods for determination of inhaled glucocorticoids in vivo and in vitro were established.With the method of wet milling and high-pressure homogenization for ciclesonide and fluticasone propionate in nanocrystalline and microcrystalline suspension was prepared.At last,we modified fluticasone propionate nanoparticles with phospholipid.The inhalable properties of five compounds were evaluated by Spraytec and NGI,and their dissolution in vitro was evaluated by an modified Transwell dissolution device.The content of drugs in bronchoalveolar lavage fluid,lung tissue,intestinal tissue and blood was measured after administration of micron and nano crystalline suspension in lungs of rats.Among them,the content of bronchoalveolar lavage fluid represents the insoluble content of the medicine.The content of the drug in the intestinal tissue represents the content of the drug which clears to intestine,and the blood represents the content of the drugs absorbed into the systemic circulation.The results showed that the content of drugs in bronchoalveolar lavage fluid was related to the dissolution of drugs in the lungs.Ciclesonide micro crystal achieved a long-time resident in the lungs.Nanocrystals can reduce lung mucociliary clearance and improve lung bioavailability.Phospholipid modified nanocrystals can reduce lung mucociliary clearance and improve the bioavailability of the drug in the lungs,and its bioavailability is 1.7 times of that of nanocrystals and 4.2 times of that of micron crystals.