Development Of Amisulpride Orally Disintegrating Tablets

Amisulpride is a dopamine D2 receptor antagonist used for the treatment of acute or chronic schizophrenia with positive or negative symptoms.It has low solubility,almost insoluble in water,and has the problem of low oral bioavailability.It belongs to BCS class II drugs.This subject aims to use solid dispersion technology to improve the low solubility of amisulpride.On this basis,an orally disintegrating tablet with good disintegration properties is prepared,and its quality and stability are investigated.Part One Preparation of Amisulpride Solid DispersionObjective: To screen out the appropriate solid dispersion carrier and carrier dosage,and prepare an amorphous solid dispersion to improve the solubility of amisulpride.Method: Screen the carrier and carrier dosage with in vitro dissolution as an indicator,optimize the preparation process through orthogonal design and verify it;use Fourier transform infrared spectroscopy(FT-IR),X-ray powder diffraction(XRD),and differential scanning volume Thermal method(DSC)and scanning electron microscope(SEM)were used to characterize the prepared solid dispersion;the taste masking effect of the solid dispersion was evaluated by the bitterness score;the stability of the preparation was investigated by the influencing factor test.Results: The most carrier of amisulpride solid dispersion is PVP K30,the ratio of drug to carrier is 1:2,the process parameters of the solvent method are reaction temperature 60℃,Stiring time 2h,evaporation temperature 40℃;The physical characterization results show that the drug and the carrier form an amorphous solid dispersion,which has a good ability to mask the bitter taste of the drug;the preparation is stable to high temperature,strong light,and unstable to high humidity.Conclusion: The preparation of amisulpride as a solid dispersion significantly improves its shortcomings of poor water solubility and effectively masks its unpleasant taste.The formed amorphous solid dispersion should be sealed when stored.Part Two Study on the formulation and technology of amisulpride orally disintegrating tabletsObjective: Through single factor investigation and screening of the prescription technology of export disintegrating tablets,optimizing and verifying,preparing orally disintegrating tablets with excellent disintegration performance and good taste.Methods: Direct powder compression was used to prepare orally disintegrating tablets,and the disintegrants,fillers,lubricants,glidants,and flavoring agents were sequentially investigated through single factors;Box-Behnken design combined with response surface methodology was used to optimize the formulation And verify the best prescription.Results: The optimal prescription was finally determined as AMS-SD150 mg,PVPP 37.45 mg,CMS-Na 51.8 mg,mannitol 58.8 mg,microcrystalline cellulose 34.45 mg,magnesium stearate 3.5 mg,talc 7 mg,aspartame Sweet 6.3 mg,vanilla essence 0.7 mg.The average disintegration time of the three batches of orally disintegrating tablets was 31.7 s.Conclusion: The preparation process of amisulpride orally disintegrating tablets is simple and feasible.The three batches of verified samples have good reproducibility and can disintegrate rapidly within 60 s.Part Three Study on the quality and stability of amisulpride orally disintegrating tabletsObjective: To study the quality and stability of amisulpride orally disintegrating tablets to ensure the safety,effectiveness and quality control of the preparation.Method: Establish a set of quality standards for amisulpride orally disintegrating tablets,including appearance,hardness,friability,taste,disintegrant time,content and in vitro dissolution.Carry out influencing factor test and accelerated test to investigate the stability of the formulation.Results: The prepared orally disintegrating tablets have a good taste and can disintegrate rapidly within 60 s;the established methodological results of amisulpride orally disintegrating tablets content determination and in vitro release indicate its system applicability,linearity,precision and repeatability Both the recovery rate and the recovery rate meet the requirements;the preparation is stable to high temperature and strong light,has certain hygroscopicity,and has good stability in the accelerated test.Conclusion: A reasonable and achievable quality standard has been established for amisulpride orally disintegrating tablets,and the preparations should be sealed and preserved during storage.