Preparation Of Perindopril Tert-butylamine Tablets

Perindopril tert-bulylamine and indapamide are both long-acting hypotensive drugs. Objectives of this paper were to prepare tablets with single perindopril tert-bulamine or its mixture with indapamide as principals. Stability of perindopril tert-butylamine and dissolution of indapamide were to be enhanced in this paper.Potentiometry was established for the content determination of perindopril tert-butylamine crude drug. HPLC method was developed for impurity detection in perindopril tert-butylamine crude drug and tablets. HPLC method was also validated for content and dissolution determination of perindopril tert-butylamine tablets as well as perindopril and indapamide tablets. The methods mentioned above are accurate, liable, convenient and rapid, which all fit the requirements of analysis.Systematic preformulation study was performed for perindopril tert-butylamine tablets preparation. The results showed perindopril tert-butylamine display wonderful solubility and good stability under each physiological pH. Its o/w partition coefficient are somewhat low and pH dependent. In the stability experiment, perindopril tert-butylamine was showed to be unstable under 60℃, and appeared to degradate slightly as far as RH 92.5% circumstance was concerned. Little degradation occured under other experiment conditions. Absorption experiment by everted gut sacs showed that perindopril tert-butylamine is mostly absorbed in duodenum, jejunum and ileum, and there is no significant difference in the absorpsion rate between each of them.Effects of various excipients on the stability of perindopril tert-butylamine was studied to aid the development of stable tablets. Based on experiments, we determined that the addition of Pregelatinized Starch and adoption of wet granulation technique was critical to the stability of tablets. Keeping this in mide, we managed to develop stable perindopril tert-butylamine tablets by granulation technique. As an alternative, we dampped mix-powder of pregelatinized starch and perindopril tert-butylamin with 35% alcohol solution, after drying, the preparation were crashed into small particles(80mesh) and directly compressed into tablets with other excipients. By stability exciperments, we found tablets prepared this way promise better stability than by afore mentioned technique. But long production period, difficulties in the manipulating following this method convinced us the former was more applicable. The results of quality and stability study showed that tablets prepared by granulation technique were stable, well quality-controlled and met the purpose and requirement of dosage form design. By preformulation study and comparing dissolution profiles of indapamide in different tablets. We found that serious adsorption effect existed between indapamide and insoluble excipients such as MCC, L-HPC and pregelatinized starch. Leading to imcomplete dissolution of indapamide from tablets comprising these excipients. So reducing adsorption effect by insoluble excipients as well as improving the stability of perindopril tert-butylamine are two key points related to the quality of tablets. By making use of previous achievements, we firstly made mix-particles of pregelatinized starch and perindopril tert-butylamine for stabilization of this drug. Then we reduced adsorption effect and improved indapamide dissolution by a combination of preparing mix-particles of indapamide and lactose, reducing the amount of insoluble excipients and adding SDS into the formulatin. The results of quality and stability study showed that dissolution uniformity of these tablets is fine and that dissolution profile can be little affected by batches. therefore, tablets prepared were worthy of further development.