| Statins (3-hydroxy-3-methylglutaryl-CoA reductase inhibitors) are widely used in the treatment of hypercholesterolemic patients to reduce risk of cardiovascular diseases because of their cholesterol lowering action. Pravastatin sodium is a significant statin as its excellent water solubility and lesser side effects. The aim of this study was to prepare an orally disintegrating tablet of Pravastatin sodium in order to mask its bitter taste in vivo and make the administration more comfortable.The Pravastatin content in the complex prepared with Alginate sodium and Calcium polycarbophil and tablets was determined by a UV method. In drug release test in vitro, the UV method were applied to assay the percentage released from the complex in distilled water and that released from the tablets in 0.1mol·L-1 hydrochloric acid solution. The HPLC method was used to determine the related substance in the stability test of the tablets.First, the complex had been successfully prepared by the coevaporation method. The influence of preparation methods and formulation factors on recovery, content, drug loading, effect of taste masking and release in vitro was investigated to pick out the best formulation, and the results showed that the taste masking complex made by it could mask the obvious bitter taste of Pravastatin sodium in mouths. The other data were: recovery>88%, drug loading>21%, the percent of release in 60min was higher than 97%.Second, the physical properties of the complex were studied, including particle flowability, compressibility and swellability. The results proved that flowability and swellablity of the complex particle between 80-120mesh were good, and the compressibility of it was so bad that under normal pressures it could not even form tablets. Then the compressibility and disintegrating property of MCC and several kinds of sugars were explored. According to the results, MCC was chosen to be the excipients to prepare the orally disintegrating tablet because of its outstandingly improving the hardness of the tablets containing the complex. That the ratio of MCC and the complex was higher than 3:5 was decided. 4.44% CMC-Na was added into the formulation as a super disintegrant. The tensile strength and the friability of the orally disintegrating tablet were about 8.0 kg·cm-2 and 0.84%, respectively. Its disintegration times in vitro and in oral cavity were about 17s and 24s, respectively. The results of the stability tests showed: the tablets were sensitive to light and humidity. So, the tablets should be tightly closed and stored in darkness.The behavior in vivo of the tablets was evaluated in six dogs after a oral administration of single dose of conventional tablets (reference formulation) or fast oral disintegrating tablets (test formulation). The pharmacokinetic parameters of the test and reference formulation were as below: Cmax were 102.5±2.9ng·mL-1 and 112.4±12.2ng·mL-1 , Tmax were 1.25±0.27h and 0.94±0.14h, MRT were 27.74±13.92h and 23.31±6.33h, the relative bioavailability was 101.4±3.9%. The results calculated by 3P87 figured that pharmacokinetic behavior of Pravastatin sodium in human conformed with two-compartment model calculated. Cmax and AUC0-t had assed analysis of variance and two one-side test and (l-2a) confidential interval test. 90% confidential interval of Cmax of test preparations compared with reference preparations was in 91.1%-112.7%. So the test and reference preparations were bioequivalence.
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