| Cough is a kind of common clinical respiratiory disease.According to the date of American Statistical Yearbook in all the cause of death,respiratory disease(not including the tumor)has risen to the third place,and seriously imperil people’s health.Levodropropizine is a peripheral antitussive drug that suitable for acute upper respiratory tract infections and acute bronchitis caused by dry cough and persisitent cough.At present,the levodropropizine used in the clinic with buccal tablet,capsule,o ral liquid,drops dosage,it has achieved good therapeutic effect,but it still taste bitter.Dispersible tablets has a lot of advantage such as it can released and absorbed quickly,it also has higher bioavailability etc.In order to solve problems of its bitter taste,the paper develop a type of taste masking tablets by means of using β-CD to include the drug.This thesis mainly includes the following content:The inclusion compound was prepared by saturated water solution method.The formulation process of the compound was optimized by orthogonal design with yield and inclusion rate as index using mole ratio of levodropropizine to β-CD,inclusion temperature and inclusion time as factors.The optimal formulation was as follows:mole ratio of levodropropizine to β-CD was 1∶1,inclusion time was 0.5 hand inclusion temperature was 65 ℃.Process validation has been done.The inclusion compounds were identified with differential thermal analysis(DTA)and X-ray diffraction(XRD).The taste of the compound was compared with that of physical mixture.Inclusion compound was confirmed to be formed by DTA and XRD.The bitter taste of the compound decreased significantly,compared with physical mixture.We use levodropropizine-β-CD inclusion complexes as intermediates in the preparation of dispersible tablets,and screen the kinds and amounts of disintegrating agents,lubricants,and wetting agents through single-factor test.Eventually determinethe prescription dispersible tablets,and its preparation process was optimized.Incorporation of disintegrating agents,granulating size,tableting pressure were screened.The final prescription of dispersible tablet is:89.6% of inclusion,10% of L-HPC,0.4% magnesium stearate.Optimization of the process is: Adding disintegrant from the outside,Preparing particles with a 24-mesh sieve,sorting particles with20-mesh sieve.The pressure for the preparation of tablets is 10-15 kg.The tablets look smoothly and they could dissolve rapidly.Formulating quality standard to levodropropizine dispersible tablets and it includes character,identification,weight,varistion,friability,uniformity,content,dissolution,related substances etc.The content of the levodropropizine were determined by HPLC.The dissolution medium,dissolution speed and stripping method was studied in the determination of dissolution.The final dissolution conditions are: The dissolution medium was distilled water.The dissolution speed is50r/min.The dissolution method is the paddle method.The dissolution medium’s content were determined by HPLC and then calculating the cumulative dissolution.Related substances was inspected by the method of principal component.The total area of each impurity peak can’t beyond 1% of the references’ main area.We see the appearance,content,dissolution,disintegration time,and related substances as the indicators to study the stability of levodropropizine dispersible tablets.The study included influencing factors test,accelerated test and long-term test.The results show that high temperature,high humidity and strong light irradiation conditions had no obvious effect on dispersible tablets dissolution.The test indexes of dispersible tablets were not changed significantly in high temperature and high humidity.The appearance of tablet yellowish slightly from white in the bright light and the content is on the decline.It illustrated that tablet is sensitive to light.So we recommended to use shading packaging material to preserve.The levodropropizine dispersible tablets’ appearance,content,related substances,dissolution,uniformity and other indexes were not significantly changed after the six-month accelerated testing and long-term trials.It shows that the stability is good.According to the resultsof stability test,we determined the period of validity is 2 years temporarily,shading and sealed when you preserve. |
