Effects Of Powder Properties And Tablet Excipients On Andrographolide Solid Dispersion Recrystallization

Solid dispersion is one or more medicinal active ingredients dispersed in a microcrystalline,amorphous or molecular form in a carrier to improve the solubility,dissolution behavior and bioavailability of a poorly soluble drug.However,the drug dispersed in the solid dispersion has a higher energy than the crystal form,and it tends to be transformed into a stable crystalline state,which causes its solubility and dissolution rate to decrease,and the advantages of the solid dispersion technology disappear.Recrystallization is the main manifestation of the instability of solid dispersions.In the study of the stability of solid dispersions,it has been found that the drug loading amount,the type of carrier,the preparation method,and the storage environment all affect the recrystallization of the solid dispersion.The carrier and the preparation method also affect the powder properties of the solid dispersion,but few researchers have considered its influence on the stability of the solid dispersion from the perspective of powder science.In addition,solid dispersions have high efficacy in improving the bioavailability of poorly soluble drugs,but the number of marketed products based on solid dispersion technology is very small.One of the reasons for this is the difficulty in developing formulations.There are few reports on the effect of formulations on the stability of solid dispersions.There fore,this article aims to study the properties of solid dispersion powders,the effects of solid dispersion tablets and tablet excipients on the relative crystallinity of solid dispersions.and to explore the key powder properties that affect the relative crystallinity of solid dispersions,and analyze the importance of key powder properties affecting the relative crystallinity of solid dispersions,The effects of preparing the solid dispersion into tablets on the relative crystallinity of the solid dispersion were also discussed.This research is helpful to improve the stability solid dispersion research system and provide new research ideas and methods for the design of solid dispersions and subsequent formulation processing.The main research contents of this article include:Using andrographolide as a model drug,using polyethylene glycol 8000,polyvinylpyrrolidone K30,poloxamer 188,and Soluplus? as carriers,the drug: carrier is in a mass ratio of 1: 4,Three methods(vacuum drying method,spray drying method,freeze drying method)were used to prepare 12 andrographolide solid dispersions.,and the powder properties of twelve solid dispersions were measured.Through variance analysis,principal component analysis,cluster analysis and partial least squares analysis,the differences and correlations between the properties of the 12 solid dispersion powders were analyzed.Studies have shown that there are significant differences in the properties of twelve andrographolide solid dispersion powders,and the preparation method and the carrier will affect the properties of the solid dispersion powders.That is,the powder properties of the solid dispersion can be changed by a controlled preparation method and a carrier.The stability and relative crystallinity of 12 andrographolide solid dispersions were investigated.Twelve freshly prepared solid dispersions were placed in an environment with a temperature of 40 ± 2 ° C and a relative humidity of 75 ± 5% for 60 days.The stability and relative crystallinity of the solid dispersions were characterized by X-ray diffraction and ANOVA was used the differences between the relative crystallinity of 12 solid dispersions were analyzed,and the effects of preparation methods and carriers on the stability and relative crystallinity of solid dispersions were discussed.Studies have shown that both the preparation method and the carrier will affect the stability of the solid dispersion,and the relative crystallinity of the 12 solid dispersions is significantly different.Through partial least squares analysis,the effect of powder properties on the relative crystallinity of solid dispersions was studied.The correlation between the powder properties of solid dispersions and the relative crystallinity was established,and the key powder properties that affected the solid crystallization of solid dispersions were determined.Hygroscopicity,particle size,and pore volume showed a positive correlation,while wettability showed a negative correlation.The stability of solid dispersion tablets and the effects of fillers and disintegrants on the relative crystallinity of solid dispersions were studied by making solid dispersion powder into tablets.The crystal stability of the tablets was lower than that of the solid dispersion,and there was no significant difference in dissolution stability.In addition,fillers and disintegrants can affect the stability of solid dispersions.