Studies On Quantitative In Vivo And In Vitro Structures Of The Enteric Coated Pellets And Their Correlations

The structure changes of dosage forms during the dissolution process determine the drug release behavior and the effectiveness of drug delivery.Therefore,a deeper understanding of the dynamic structure of dosage forms during the dissolution is of great significance for the development of the pharmaceutics.However,the quantitative determination of the structure of the traditional preparations is not enough,and little attention has been paid to the structural changes and their effects during the release process.At present,most studies on the structure of the preparation focus on the in vitro stage,and the in vivo study is relatively rare.To a large extent,the structure of the preparation in the release medium in vitro may be inconsistent with in vivo,which can not reflect the real structure of in vivo dosage forms.It is very important to obtain the dynamic structure variation of the preparation both in vivo and in vitro.In this research,three dimensional(3D)structural information of esomeprazole magnesium(ESO)and omeprazole magnesium(OME)enteric-coated pellets both in artificial dissolution media and in gastro-intestinal tract of rats were obtained by Synchrotron Radiation X-ray micro Computed Tomography(SR-μCT).Meanwhile,the structures of pellets were reconstructed and quantified.More importantly,this research optimized the conditions of in vitro dissolution from biological and physical biomimetic perspectives,so that the conditions of in vitro dissolution can better simulate the in vivo environment.The results showed that the structure parameters of ESO and OME pellets in vivo,such as sphericity,pellet volume,pore volume and porosity,were differed distinctly from those in vitro compendium media.Herein,optimizations of the dissolution media were performed to mimic in vivo conditions by introducing pepsin and glass microspheres in media and the consistency of the structure of the preparation in vivo and in vitro was used as a criterion to evaluate the optimized dissolution media.Therefore,the in vitro test results could better guide the situation of the dosage forms in vivo.The sphericity,pellet volume,pore volume and porosity of the in vivo ESO pellets in stomach for 2 h were recorded 0.47,1.55×10~8μm~3,0.44×10~8μm~3and27.6%,respectively.After adding pepsin and glass microspheres,the above parameters in vitro reached to 0.44,1.64×10~8μm~3,0.38×10~8μm~3 and 23.0%,respectively.The quantitative results of structural parameters in vitro and in vivo were very similar.Meanwhile,OME exhibits structural agreement in vivo and in vitro similarly.This study revealed the differences in the structure of oral solid dosage forms during dissolution in vivo and in vitro,and the structural features of pellets between in vitro media and in vivo condition were bridged successfully in terms of 3D structures to ensure better design,characterization and quality control of advanced oral solid dosage forms.