Quality Study On Valsartan Solid Dispersion And Tablets Preparation

Valsartan is a new anti-hypertensive drugs which is Angiotensin II receptor antagonist. Not only overcome dry cough and angioedema, making of the angiotensin converting enzyme inhibitors, but also protect the heart function, kidney function and brain functions. Through various hypertension animal model in vivo tests are given to show that valsartan is effective to anti-hypertensive and is not obvious effect on heart systolic function and heart rate. It is not produce anti-hypertensive effect on blood pressure normal animals. Blood pressure begin to decline after patients take it 2 hours. The largest anti-hypertensive effect after take it 4 ~ 6 hours.But one of the shortcomings of valsartan is poor solubility in the physical and chemical properties. It leads to a reduction in bioavailability.Solid dispersion has many advantages as drug carriers. Insoluble drug highly dispersed in the water-soluble matrix and increased the drug specific surface area.It increase the drug solubility and improve the bioavailability of the drug.To increase drug solubility and improve the oral bioavailability, this preject is prepared to prepare valsartan-loaded solid dispersion. Solid dispersion loading valsartan were prepared with PEG6000 by solvent method. the valsartan tablets were prepared by solid dispersion. The main methods and results were as follows:1. this preject established a method for the determination of valsartan's content with UV. The small glass method were used to measure the valsartan-loaded solid dispersion dissolution. The research show that UV method can be used to determine the content of valsartan-loaded solid dispersion.2. this preject established a method for the determination of valsartan's content with HPLC. The stirring paddle method were used to measure the valsartan tables dissolution. The research show that HPLC method can be used to determine the content of valsartan tablets.3. To evaluate the effects of the preparation methods, support kinds, the weight ratio of PEG6000 to drug, bath temperature,stirring time and freezing time on the dissolution of valsartan-loaded solid dispersion. On this basis,the effects of the weight ratio of PEG6000 to drug,bath temperature,stirring time and freezing time were studied by orthogonal design. The use of orthogonal design has been optimized for the prescription and processes and indicated the optimized Parameters. The weight ratio of the PEG6000 to drug was1:5. The bath temperature was 75?. The stirring time and freezing time were 10 min and 40 min. The composition of prescription was reasonable and preparation process was stable. Through the infrared scanning,DSC and dissolution make the optimal prescription quality evaluation. The results of the experiment that the preparation of valsartan solid dispersions conform to the requirements.4. The project to select the preparation of adhesive, filler and disintegrating agent in valsartan tablets by single factor. On this basis,the effects of the weight ratio of disintegrants,disintegrants join to method and hardness were studied by orthogonal design. The use of orthogonal design has been optimized for the prescription and processes and indicated the optimized Parameters. The weight ratio of disintegrants was 8%.The disintegrants join to method was interior addition. The hardness were 60 N. The composition of prescription was reasonable and preparation process was stable. On the optimal prescription of valsartan make a series of quality tests.The experimental results show that the tablets difference, hardness, dissolution and content uniformity are all conform to the requirements of the Chinese Pharmacopoeia.