Studies On Compound Acetaminophen Orally Disintegrating Tablet

Object:It is a wide-accepted combination of acetaminophen, pseudoephedrine hydrochloride and dextromethorphan hydrobromide to cure common cold and which has been proven to be effective and very safe through wide-range and long-term clinic application, so it is suitable to be prepared into orally disintegrating tablets (ODT) for children use. However, all of the three components have bitter taste, to be a children-use medicine; Unfavorable bitter taste will significantly affect the compliance of patient to take the medicine. To deal with this problem, only adding sweeting agent into the formulation will not achieve ideal effect. So we do the study to solve the problem taking advantage of modern bitter-masking technology.Methods and results:1. According to the analysis of present bitter-masking technological methods, we decided to adopt the drug substance granule coating method, first granulate the principal agent into microparticles, then coat the microparticles.The coating material is a kind of material that won't rapidly dissolve in oral cavity but will rapidly dissolve in stomach basing on its pH-dependent dissolubility. Because of its special property, the coating film can be maintained undissolved in oral cavity in certain time, thereby mask the unfavorable taste of the drug substance. Entering into the stomach, the coating film will dissolve in the acid gastric juice and release the active substance. Using bitter-taste masking rate and effective coating yield as index screen out the optimized formulation through studying on the crucial process parameters such as formulation and density of coating solution, coating increment and coating temperature. Moreover, have researched on the antistick layer for fear of the coated microparticles stick-together. According to the CDE conference summary about ODT on Aug. 2nd,2003, and with reference to disintegration-time determinator set in pharmacopoeia, designed the test method of disintegration time for ODT, and testified this method can mimic oral condition and has good reproducibility, and can be used as effective method to inspect disintegration time and particle size; At last, obtained optimized ODT formulation.2. Have done quality control study towards the obtained ODT sample. To control the impurity and degradation in the preparation,we took advantage of HPLC to do corresponding method study. Using two chromatographic systems to investigate relevant substance in acetaminophen, pseudoephedrine hydrochloride and dextromethorphan hydrobromide. What's more, have done experiments to investigate content, dissolution rate and so on.3. Stability investigation on the ODT Sample. The conditions: high temperature(60±2℃), high humidity(RH 75±5%&RH 90±5%), illumination(4500±500LX); and completed 6 months accelerated test and 12 months long-term test. The result show that except showing moisture absorption under high humidity(RH 75±5%和RH 90±5%)condition, the ODT samples remain stable under highlight and high temperature(40℃,60℃) and in accelerated test as well as in long-term storage test.