The Formulation And Manufacture Process Research Of Telmisartan/Hydrochlorothiazide Tablets

In this study,we obtained a coated Telmisartan granules by fluidized bed,mixed well with Hydrochlorothiazide granules and compressed into single layer-tablet.With the deeply studies on formulation and manufacturing process,the final formulation was determined.1.Formulation development of Telmisartan/Hydrochlorothiazide TabletConfirmed by the specification of hydrochlorothiazide stability,content uniformity and ploit bioequivalence trials,it’s show the best formulation was with 14.4 mg carboxymethyl cellulose calcium,8.5 mg NaOH,82.7 mg mannitol,40 mg corn starch in the Telmisartan granule with coating weight was 3%,and with 58 mg carboxymethyl cellulose calcium,181.6mg microcrystalline cellulose,58 mg corn starch,5.8mg magnesium stearate in the Hydrochlorothiazide granule.2.Manufacturing process development of Telmisartan/Hydrochlorothiazide TabletThe optimization of manufacturing process was performed with the final formulation by pilot scale.The results showed that with a blend time more than 25 min,the blend uniformity were 99.8%and 100.1%for Telmisartan and Hydrochlorothiazide,respectively,with relative standard deviation(RSD)of 0.7%and 1.1%which was in accordance with related specification.And there were no significant difference in dissolution with a tablet hardness range of 10 kp-13 kp.Three pilot validation batchs had the average content of telmisartan and hydrochlorothiazide was between 97.2%-99.3%and 99.7%-102.8%,respectively.The impurity B of Hydrochlorothiazide and total impurities accounted for 0.11%-0.14%and 0.33%-0.41%of samples,respectively.The three batchs dissolution had no significant differences in three mediums.In conclusion,we have developed a tablet formulation and manufacturing process that ensures the quality and efficacy.3.Bioequivalence trials of Telmisartan/Hydrochlorothiazide TabletA bioequivalence trials with 36 cases was performed in Moldova with a batch of pilot product by ALFRED E.TIEFENBACHER(GMBH&Co.KG).With a confidence interval of 90%,the area under the curve(AUC)is 96.06%-110.30%and 93.66%-102.31%for telmisartan and hydrochlorothiazide,respectively.While Cmax is 84.04%-108.76%and 83.11%-99.00%,respectively.All the results were in accordance with the bioequivalence standard of 80%-125%.