Pharmacy Research On The Preparation Of Orally Disintegrating Tablets By Phase Transition Method

Objective:The purpose of this research is to investigate the excipients and the factors affecting the preparation process of orally disintegrating tablets by phase transition method,to provide a research basis for the preparation of orally disintegrating tablets by phase transition method,and to provide an effective reference for the application of phase transition method in the field of pharmaceutical formulation.Methods:The orally disintegrating tablets were prepared using phase transition method.Xylitol,sorbitol,lactitol monohydrate and lactitol dihydrate were selected as low melting point phase transition materials,and the effects of phase transition materials,fillers,disintegrants and lubricants on the quality of orally disintegrating tablets were investigated using the hardness,disintegration time,fragility,wetting time,surface morphology and porosity of orally disintegrating tablets before and after phase transition as the main indexes.Metoprolol tartrate was selected as the model drug to investigate the effect of phase transition method on drug dissolution of the formulation.In this study,suitable excipients and processes were screened by singlefactor test and optimized using Box-Behnken Design response surface method.Results:The effect of xylitol and sorbitol on the quality of orally disintegrating tablets after phase transition was better than that of lactitol monohydrate,and lactitol dihydrate was not suitable for the preparation of orally disintegrating tablets by phase transition.The effect was better with 15% of lactitol monohydrate,and the hardness of orally disintegrating tablets increased from 15 N to about 30 N after phase transition,and the disintegration time was extended from 15 seconds to 35 seconds.The porosity doubled,and the fragility of tablets slightly decreased.Three phase transition materials,xylitol,sorbitol and lactitol monohydrate,did not affect the dissolution of drug after phase transition.Among the selected sugar alcohol fillers mannitol had better compressibility and better quality improvement of orally disintegrating tablets after phase transition.Among the selected non-sugar alcohol fillers,the hardness of orally disintegrating tablets prepared from trehalose could be increased up to 6 times after phase transition,but their disintegration time exceeded the disintegration time limit.Polyvinylpolypyrrolidone(PVPP)was more effective in the phase transition method,and the xylitol and sorbitol orally disintegrating tablets of PVPP could disintegrate completely in about 10 seconds after the phase transition,and the hardness was increased from 15 N to about 40 N.The hardness of orally disintegrating tablets prepared with sodium carboxymethyl starch(CMS-Na)was basically doubled to about 30 N after phase transition,and the disintegration time was basically unchanged at about 20 seconds.Low-substituted hydroxypropyl methyl cellulose(L-HPC)is not suitable for use in the phase transition method,and the prepared orally disintegrating tablets disintegrated slowly after the phase transition.Croscarmellose sodium(Ac-Di-Sol)is suitable for orally disintegrating tablets prepared by sorbitol phase transition.After sorbitol phase transition,the hardness of orally disintegrating tablets increases to 40 N and the disintegration time is around 30 seconds.The quality of orally disintegrating tablets prepared with sodium stearyl fumarate and magnesium stearate was significantly improved when the heating time was less than 10 minutes,and the heating time over 30 minutes prolonged the disintegration time of orally disintegrating tablets after phase transition.Conclusion:The phase transition method can significantly improve the hardness and porosity of the tablet,reduce the disintegration time and fragility of the tablets.The phase transition method has no effect on the drug dissolution,the drug can be completely dissolved in 3 ～ 5 minutes.The effect of 5% xylitol and sorbitol in orally disintegrating tablets prepared by phase transition method was the best,and the hardness of the tablet was up to 60 N,which was three times of the hardness before phase transition.The essence of phase transition method to improve the quality of the orally disintegrating tablets is the result of the joint action of the diffusion,bonding ability and porosity of the phase transition materials on the orally disintegrating tablets.This study provides an experimental basis for the selection of phase transition materials by phase transition method.