The Study On Preparation Technology And Quality Standards Of Qinghouliyan Buccal Tablets

Objective :To optimize extraction process of Qinhou Liyan buccal tablets,establiash its quality standard, research its stability and initial pharmacodynamics,to provide scientific theory basis for the preparation of the production packging storage and use.Methods:(1) Based on pre-experiments,effects of soaking time,solvent dosage and extracting time on overall desibirability of contents of chorogenic acid and totale flavonoids(included rutin,liquiritin and luteolin-7-0-glucoside)were investigated and forcecasted by response surface metholodgy. HPLC condition: HPLC was performed on XTerra C18 chromatographic column(4.6 mm×250 mm, 5 μm) with a gradient elution system,using acetonitrile(A)-0.5% phosphoric acid(B)(0 ~ 12 min, 9% A; 12 ~ 15 min, 9% ~ 15% A; 15 ~ 40 min, 15-45% A; 40 ~ 50 min, 45% ~ 15% A; 50 ~ 80 min, 15% A),at a flow rate of 1.0 m L· min-1, and at 30 ℃. The eluate was detected by wavelength of 327 nm for chlorogenic acid and 265 nm for three flavonodis.(2) The optimum forming technology of different excipient ratio was optimized using the appearance,taste,crushing strength and disssolution time as the evaluation index through single factor experiments combined with orthogonal tests.(3) A TLC method was set up for the identificaation of flos lonicerae,radix scrophulariae,radix ophiopogonis,radix glycyrrhizae.We detected the weight variation,disintegration time,hardness and the content of chorogenic acid of small enperimental product. Meanwhile,we carried out Influencing factor experiment and classical constant temperature acceleration experiment of small experiment product.(4) Acute toxcity and anti-inflamatory experiment were carried with Kunming mouse.The mouse’s acute pharyngitis model was established on Wistar mouse. Results:(1) The fit of the model was 0.9434. The optimum water extracting technology is: The optimal reflux extraction parameters of lonicera japonica、liriope spicata、fructus chebulae immaturus 、 scrophularia ningpoensis 、 dark plum fruit 、 platycodon grandiflorum 、 glycyrrhiza uralensis were soaking time—120 minutes, material ratio-16.4:1,reflux extraction time-two times,39.2 minutes per time. Chlorogenic and three kind of flavonoids respectively showed a good linear relationship between their linear range. Average recovery were respectively 99.97%, 100.77%, 102.86%, 98.61%. RSD were 2.08%、2.55%、2.10%、2.50% seperately.(2) The best molding process of buccal tablet was : 75% prescription extracts,25% diluent(iactose-mannitol 2:1) and stevioside including 5% prescription extracts and diluent, screened 100 meshes,well mixed,then made soft material by the pure ethanol,pelleted(2 mesh),and dried at 60℃ for 120 minutes.Then granulated(2 mesh),added oleum menthae and 2% magnesium stearate,and compressed tablets.(3) The test of influencing factors indicated that Chlorogenic acid was sensitive to sunlight, air and moisture and and was easy to be degraded and absored moisture. The determination of classical constant temperature method was used for five months.(4)The dose group, and the positive contrast group had signicificant difference.Between the dosage group and the positive group,there was no significant difference.Conclusions:(1) The established mathematical model whose stability was well can be used to predict. HPLC condition is available to quantitative determination of Chlorogenic Acid and three flavonoids.(2) The prescription and preparation technics of Qinghouliyan buccal tablets is reasonable, which can be adaptive to the requirement ofindusty(3)The buccal tablet should be sealed, avoid light, placed in a cool ventilated place, in order to prolong the period of validity.(3) Acute toxicity experiment shows that the qinghouliyan buccal tablet daily dosage was safe.(4) Anti-inflammatory experiments showed that Qinhouliyan buccal tablet have the function of the intervention of acute inflammation.