Characterizations Of Roxithromycin APIs From Five Manufacturers And Their Pre-formulation Study

At present,the vast majority of drugs used in clinical practice in China are generic drugs and they account for 70~80% of the market.However,the quality of generic drugs has not been effectively monitored for a long period.Problems still exist in many stages,range from raw materials to the final declaration,resulting in the uneven quality of generic drugs in our country.So,it is difficult to achieve real improvement in both preparation and technology aspects.In this work,roxithromycin APIs produced by five different manufactures were characterized,using X-ray powder diffraction,scanning electron microscopy,differential thermal-thermogravimetric analysis,infrared absorption spectroscopy,melting point,particle size,solubility as well as stability.Applying these methods above,different crystal forms of roxithromycin were identified and classified and it was found that though the APIs available in the market have reached the required chemical standards,the quality of state of matter,particle size,etc.were difficult to be unified.On the basis of obtaining these diverse dates,an identical prescription was used to prepare the APIs into tablets.Influence of preparation on the APIs' crystal form was examined.Factors that affecting the quality of final formulation product were also looked into by dissolution method.After different crystal forms of roxithromycin APIs compressed into tablets,they exhibit different dissolution behaviors.This experiment reveals the importance of pre-formulation studies before developing a formulation and provides scientific basis for the selection and the quality control of roxithromycin API's dominant crystal form.In addition,three hydrophilic carriers of polyethylene glycol 4000,polyethylene glycol 6000 and povidone K30 were used as carriers for solid dispersions.Melting and solvent methods were selected to prepare roxithromycin solid dispersions.The results show that roxithromycin mainly exists as co-polymer or amorphous form in polyethylene glycol materials,and it presents in amorphous form in povidone K30.At the carriers' ratio of 1:1,1:2 and 1:4,dispersion samples can effectively increase the solubility of roxithromycin.Furthermore,X-ray powder diffraction was directly used to test the stability of all sample within 30 days under high temperature(45 ?)as well as high humidity(75%RH)conditions.The experimental results show that polyethylene glycol is unable to inhibit the growth of roxithromycin crystal under neither high temperature nor high humidity conditions.However,as the carriers' proportion increase,the effect of inhibition gradually enhances.As thermal stability of povidone is excellent,roxithromycin can preserve in amorphous form for 30 days at high temperature condition.Yet,properly due to its hygroscopicity or high energy molecular state,when samples placed in high humidity condition,crystalline diffraction peaks appear gradually.This article conforms that both melting and solvent methods can be used to prepare roxithromycin dispersion,and the selection and proportion of carriers need further studies.