Preparation And Characterization Of Tinib Nano-Formulation For Leukemia Treatment

The tinib are tyrosine kinase inhibitors.This article deals with two types of tinib drugs:dasatinib and nilotinib.They mainly exert anti-leukemia effects by inhibiting the BCR-ABL fusion protein.Dasatinib is a BCS II drug,nilotinib is a BCS IV drug.Both of them are insoluble and have very low solubility in water.Therefore,it is particularly important to increase the water solubility of drugs and increase the bioavailability of drugs.After the drug particles reach the nanoscale,the dissolution of the drug is significantly increased,and the resistance to transmembrane transport is also reduced.Therefore,the bioavailability of the drug can be improved.In this paper,tinib nanoparticles and composite powders were prepared by anti-solvent precipitation method,and the composite powder was used to prepare nano-tablets.The effects of solvent/anti-solvent volume ratio,excipients,system temperature,stirring speed,and other factors on the particle size and morphology of the granules were investigated.XRD,FTIR,DSC characterization and dissolution test were conducted.The friability qualified and the dissolution of the tablets in different dissolution media in vitro were examined.The main conclusions are as follows:Using DMF as a solvent and water as an anti-solvent,under the experimental conditions of a volume ratio of S/AS of 1:20 and a drug concentration of 50 mg/mL,rod-shaped particles having an average minor diameter of 300 nm with length-diameter ratio of 3?6 can be prepared.After spray drying and lyophilization,flake particles of about 1?m were obtained and the dissolution rate reached about 65%.The effects of excipients on particle morphology and particle size were investigated,and mannitol was selected as a excipient.The mass ratio of dasatinib to mannitol is 1:1,dasatinib composite powder with a particle size of less than 1 ?m can be prepared,and the drug dissolution reaches 90%.FTIR,XRD and DSC tests showed that the chemical structure of dasatinib in the composite powder before and after preparation did not change,and the crystalline form of dasatinib was still N-6 crystal form,but the crystallinity was reduced.After the composite powder was stored at 25 ? for 120 days,its crystal form,composition and dissolution did not change,and the composite powder was stable under room temperature and dark conditions.Tablets were prepared using composite powders,tablet formulations were determined,and dissolution tests were performed in different dissolution media.The results showed that in the pH 4.5 buffer solution,the initial dissolution rate of self-made nano-tablets and commercial tablets were basically the same,but the final dissolution rate of self-made nano-tablets after 15 minutes was 96%,which was 15%higher than that of the commercial tablets.In the buffer solution of pH 6.8,the dissolution rate of the commercial tablets was maintained at approximately 6%after 15 minutes,while the dissolution rate of the self-made tablets reached 11%within 15 minutes to 45 minutes,which was 5%higher than that of the commercial tablets.This shows that the dissolution performance of dasatinib nano-tablets is significantly better than that of commercial tablets.During the preparation of nilotinib nanoparticles,SDBS was added to increase the stability of the system,DMF was used as the solvent,water was used as the anti-solvent,the drug concentration was 15 mg/mL,TPGS was added,and the ratio of drug excipients was 1:0.2.It can produce a more stable nilotinib nanosuspension with a particle size of about 300 nm.