Preparation Of Simvastatin Orally Disintegrating Tablet By Solid-States-Dissolution Technology

Orally disintegrating tablets(ODT for short) is a special kind of tablet, it can disintegrate(15~30s), disperse or be dissolved in saliva rapidly without any water or with an extremly small amount of water. With only a few swallowing acts, patients can finish the process of taking medicine. Therefore, it has many advantages, convenience of taking medicine is the most prominent one. It is particularly applicable to patients who have difficulty in swallowing as well as the elderly, children and patients who need long-term medication so as to improve patients'compliance of taking medicine. The development of ODT is so rapid in recent years that more and more domestic and foreign scholars are paying great attention to it.The experiment regards simvastatin as a model drug. Simvastatin is HMG–CoA enzyme inhibitor and it is a neotype of blood liquid regulation drug which can be applied to the therapy of hypercholesteremia and coronary heart disease clinically. The drug can decrease death risk which is caused by coronary heart disease and nonfatal myocardial infarction ,reduce myocardial revascularization operations and delay the development of atherosclerotic.Orally disintegration tablet which is made from simvastatin can disintegrate into uniform suspension in water so that it has the features such as easy administration , rapid absorption, suitable for elderly patients'long-term administration and elevating patients'compliance. Many preparative method can be applied to produce orally disintegration tablets.For example, lyopyilization, direct compression, spray drying,flash technology and solid state solution technology ,etc. This experiment prepares simvastatin orally disintegration tablets by solid state solution technology which has been comparatively less studied in China,this technology is particularly suitable for thermosensitive drugs , and the tablets which are made bysolid state solution technology can disintegrate rapidly in water(5～10s).Modify method for in vitro determination of orally disintegration tablets'disintegration time and compare it with other determination methods so as to establish determination method of disintegration time of orally disintegration tablets. The result indicates self-made method can imitate oral physiological enviroment of human, the value of R is 0.007 with measurement, in vivo-in vitro correlation is relatively good, the disintegration time of test tablets is about 7s.Tablets which are prepared by solid state solution technology are high pore matric tablets. The magnitude of interval porosity is an important factor which effects disintegration time. Determine apodemal interval porosity of orally disintegration tablets with liquid displacement method and then investigate the relationship between interval porosity and disintegration time of tablets, the result indicates they are in a reverse relationship with each other.Regard formability of tablets as an index to determine the formation of orally disintegration tablets'skeleton matrix agent in suitable range and then evaluate orally disintegration tablets according to their disintegration time. Optimize the prescription further with factorial design experiment.The determined basic prescription of orally disintegration tablets is as follows:manicol 1.5%,gelatin 3.0%,aspartame 0.1%,water95.4%. Prepare simvastatin orally disintegration tablets by solid state solution technology, common melting point of the solution is -9℃via temperature resistance method.Regard formability of tablets as evaluation criterion and choose pre-freezing temperature -40℃as suitable temperature requirement, exchange temperature of solution is -15℃. Formability of blank matrix tablets which are prepared by self-made experimental facility is comparatively good, phenomenons such as collapse and atrophy are rare.With application of HPLC method, added drug loading of principle agent at various concentration in different time is investigated, from the result, we can see the added drug loading of principle agent after the preparation of blank matrix tablets is more than that is added before the preparation.The drug loading of simvastatin solution at 10mg/ml concentration is found to be the most according to the experiment, its average drug loading is 83.9%. The content of Simvastatin-ODT is 97.8%,common tablet is 98.5%. The disintegration time of common tablet is slower than ODT (<40 min ).At 5min, the dissolution rate of orally disintegration tablet has achieved 79.5% in phosphate buffer-n-propyl alcohol ,and at 30min, it is higher than 90%,demonstrating that the prepared orally disintegration tablets can release rapidly in vitro.Investigate primiary stability of tablets of different batches, the result indicates the tables are high temperature resistant and light resistant, but their preservation should be moisture proofing.