Isosorbide Mononitrate (5-ismn) Orally Disintegrating Tablets

Isosorbide 5-mononitrate (5-ISMN) is one of the nitrates to treat deplethoric angiocardiopathy. Like other nitrates, its major pharmacological function is to laxitize vascular smooth muscle. Its application has become a worldwide practice soon after its releasing in West Germany in 1981. China started to import 5-ISMN preparation in 1988. and started to make its producer goods and troches in 1994. Through oral application, 5-ISMN can be assimilated very fast with no First Pass Effect. Its plasma concentration reaches the peak in 30 to 60 minutes. And its bioavailability is 100 per cent. Moreover, its valid plasma concentration has the advantage of being stable and long drawn.The study has chosen 5-ISMN as its target medication, with MCC and L-HPC as disintegrant to make orally disintegrating tablets. Sopped up in water. L-HPC has a dilatability rate 10 times faster than that of MCC. Thus, with the right mixture, the objective of a rapidly releasing tablet with minimum disintegrating time can be achieved.In order to make the rapidly releasing tablets, direct-power-press method was adopted. And the orthogonal design was chosen to screen out the right recipe. With indicators of tablets collapse rate and dissolving percentage in 30 seconds, investitive weight at 60% and 40%, comprehensive scores were enumerated in order to screen out the best recipe. As a result, the optimal recipe is: MCC and L-HPC mixture ratio at 8∶2 (32%. 8%). CCNa at 3%, mammitol at 15%, andα-lactose at 31%. The tablets made with such a recipe could not only fully integrate in 20 seconds releasing 80% of the medication in 1 minute but also taste good. Further more, the study included a research on stirring speed in the process of making the tablets.In order to determine 5-ISMN plasma concentration, HPLC was adopted. This method has the advantage of being most sensitive, most easily handles and best serving the purpose. Within the range of 31.25ng/mL and 2000ng/mL, this method has the best linearity correlation. Based on such a method, human experiments were carried out on healthy volunteers. The testees were given normal 5-ISMN tablets and the rapidly releasing tablets in order to study the pharmacokinetics and bioavailability behind the tablets. The result shows that both tablets" movement in human body was in accordance with One-Compartment Model. In comparison to normal tablets, the rapidly releasing tablet has the bioavailability rate of 94.73%, and can be a biological equivalent to normal tablets. Moreover, the rapidly releasing tablet reaches its peak in 26.52 minutes, which is comparatively much faster than normal tablets 95.73 minutes. Thus. the rapidly releasing tablet works better in emergency.To sum up, the study has not only made way for 5-ISMN in clinical application. but also produced a new-fashioned orally disintegrating tablet.