Study Of Cilostazol Tablet Prescription And Quality

Cilostazol, an ideal anti-platelet aggregation drug, was firstly manufactured by Japanese Otsuka Pharmaceutical Co Ltd in 1988 and clinically applied in Japan, and it was approved by FDA on May 1999 and it landed China in 1996. Featured with low toxicity and high safety and new coming clinical explicabilities, there is an increasing demand for cilostazol. Though there are more than 20 companies including the Zhejiang Otsuka Pharmaceutical Co Ltd, manufacturing the tablets of cilostazol, the price of this drug is still relatively high. Besides, the quality control method of the tablets of cilostazol is backward. For example, the ultraviolet spectroscopy is applied in the content measuring of this tablet. So this research aims to screen the accessories to develop the cilostazol tablet with cheap cost and use HPLC to measure the content of the main drug of the newly made-up tablets, leading to enhance the quality control of this tablet.This paper design a kind of new cilostazol tablet and screen to confirm the type and corresponding amount of filler, disintegrant, lubricant and adhesive according to the physicochemical property of cilostazol, the prescriptions of cilostazol tablets which have been in the market and domestic market availability of the corresponding accessory. This tablet uses starch as filler, polyvinylpolypyrrolidone as disintegrant, magnesium stearate and aerosol as lubricant, and 5%PVP50% ethanol as adhesive. Compare with the existing tablet in the market, this tablet owns the advantages such as simpler formulation composition, cheaper cost of the accessory and so on, resulting in reducing the manufacturing cost significantly, meanwhile, the quality of this tablet could reach the demand of the marketing products. In the experiment of the content measurement, HPLC, which is more efficient in specificity, is applied in test, resulting in more accurate in testing the main drug and more selective telling from the impurities.The researching of technology of prescription is to screen the prescription, and draft the plausible prescription and preparation technology of cilostazol tablet according to the properties and liquidity before and after the dry of article, the appearance, hardness, formability, rigidity, slaking and dissolution of the tablet as the index. By screening the results, the optimized prescription was as follows:every single tablet contained cilostazol 50mg, starch 48mg, polyvinylpolypyrrolidone 10mg, magnesium stearate 3mg, aerosol 5mg and certain amount of 5%PVP50% ethanol. Wet granulation technique, featured with simple preparation technology, cost effective, was employed to make the cilostazol tablet and could reach the demand of WSl-(X-001)-2001Z for the cilostazol tablet quality control. Besides, through making a comparison between dissolution curve of the new tablet and of controlled tablet, the results revealed that the new tablet had better quality than the market demands.The quality research part mainly processed the validation of methodology of content, dissolution, the related substances of cilostazol table by the high performance liquid chromatography, and figured out whether the new method could be applied to the new tablet. The results showed that:1. in the experiment of confirming the content, cilostazol was in good linear relationship between 60～140μg/mL and the limit of the quantitation was 8ng/mL, and the limit of detection was 1.6ng/mL, the average recovery was 98.84% and this method was simple, precise, highly specific and accurate; 2.in the experiment of confirming the dissolution, the dissolution medium, volume, method and rotate speed were investigated respectively, the cilostazol table had good dissolution rate reaching 96.6% in 30 min which met the demand of the draft by using 500mL0.3%SDS as dissolution medium, oar methods as method and 75 r/min as rotate speed; 3. in the experiment of confirming the related substances, cilostazol was in good linear relationship between 1.5～3.5μg/mL and the limit of detection was 1.6ng/mL, and the limit of the quantitation was 8ng/mL, and this method was sensitive, precise, highly specific. All the results demonstrated that this method was suitable for the quality control of cilostazol table.The main goal of the comparison of the dissolution profile part was to investigate whether the quality of this new tablet could reach the demand of market products and to accumulate data for the bioequivalence experiment. We used five different dissolution media (0.3%SDS, water, pH1.0 HC1, pH4.0 phosphate buffer, pH6.8 phosphate buffer) to compare the dissolution curve between the new tablet and the controlled one, using f2 factor method to judge similarity in dissolution characters. The results revealed that dissolution profile of the two tablets were nearly the same in the five dissolution media, suggesting that characters of absorption, distribution and metabolism of this new tablet in the body had reached the quality standard of the market products.The research on stability part mainly did the stress test, accelerated test and long-term investigation on cilostazol tablet. The results revealed that the appearance, properties, weight variation, content, dissolution and the related substances of the cilostazol tablet did not process a significant change during the test and the results also met with the demand of the draft. However, slight inflation occurred to some samples which were put in the high humid environment, suggesting that this tablet need to be kept in dry environment. Besides, through the accelerated test and long-term investigation on the stimulated commercial packaging of cilostazol table, no cracked or broken tablets were found and the quality was relatively stable and the content, dissolution, the related substances were complied with the draft, indicating that cilostazol table was stable in that package.