Study On The Formulation And Process Of Compound Tablet Containing Diphenhydramine Citrate Pellet

Advil~?PM is a kind of bilayer tablet containing diphenhydramine citrate and ibuprofen,and it is widely used in the treatment of insomnia accompanied by mild pain.Owing to the potential compatibility reaction between diphenhydramine citrate and ibuprofen,the original drug was prepared as bilayer tablet to avoid the ocurrence of compatibility reaction.However,the bilayer tablet could not totally separate the drugs,in order to reduce the contact of drugs in the interface,this paper prepared a kind of tablet containing pellet,which is composed of coated diphenhydramine citrate pellets and ibuprofen particles,and discussed the feasibility of avoiding compatibility reaction by coating isolation technology,to provide the experimental basis and technical reference for the subsequent comprehensive imitation study.Objective:to prepare diphenhydramine citrate pellet and compound tablet containing diphenhydramine citrate pellets,and investigate the formulation and process factors affecting the quality of diphenhydramine citrate pellet and compound tablet containing diphenhydramine citrate pellets(shape of coated pellets and the content uniformity of drugs)respectively;to explore the stability of self-made tablet containing pellet under the conditions of light,high temperature and high humidity,and study the feasibility of avoiding compatibility reaction by coating isolation technology by comparing with original tablet.Method:the fractional factorial design combined with central point was used to analyze the main formulation and process factors affecting the quality attribute of pellet(yield,disintegration,roundess);The coated diphenhydramine citrate pellets from various locations at the axial and radial peripheral surfaces and core of the tablet containing pellet were excavated and assessed for their coat damage individually;the content uniformity of tablet containing pellet prepared by different particle size distribution(250?m~450?m:450?m~600?m:600?m~800?m=1:1:1?1:2:1 and 1:3:1)and range were determined by high performance liquid chromatography;the changes of water,appearance,the drug content and the impurities of compound tablet and original drug were explored under the guidance of the stability test guidelines of raw material medicine and formulation in general notices of ChP2015.Result:the formulation factors(the amount of MCC and SDS and the concentration of PVP-k30)have significant effect on the quality attribute of pellet;the coat damage of pellet at different location is in the order:radial peripheral surface(45.54%)>axial peripheral surfaces(21.12%)>core(16.08%);the content uniformity of tablets prepared by different particle size range is in the order:250?m~450?m>450?m~600?m>600?m~800?m>250?m~800?m;the total impurity of both original tablet and tablet containing pellet increased under the condition of light,high temperature and high humidity,but the total impurity growth rate of original tablet is higher than tablet containing pellet.Conclusion:avoiding the contact between pellet and pellet,punches is beneficial for the completeness of pellets;in a large particle size range,the change of particle size distribution is not an effective way to enhance the content uniformity;reducing the particle size distribution is beneficial for enhancing the content uniformity and the smaller the particle size is,the better the content uniformity is;the coating isolation technology can avoid the contact of diphenhydramine citrate and ibuprofen effectively,thus reducing the compatibility reaction between them.The tablet containing pellet is sensitive to light and high temperature,and has great hygroscopicity,so it needs to be preserved in tight containers at controlled room temperature.