Improvements On The Key Tableting Properties Of Pueraria Lobatae Radix Extract Powders By Porous Design

Objective:This study aimed to address the tableting problems of the extracts of traditional Chinese medicine（TCM）,like poor compactibility and slow tablet dissolution rate,by designing porous TCM particles with improved key tableting performances,which may expand the application of the dosage form‘tablet’in TCM.Methods:Firstly,the suitable model drug,pore-forming pattern,and porogen were selected by taking compactibility and disintegration time/dissolution rate as indicators.Secondly,the in-and-out pore-forming method and the surface pore-forming method were studied in detail,and the powder properties and tablet properties of the model drug before and after pore forming were compared.Lastly,the stability and applicability of porous particles prepared by the surface pore-forming method were studied due to their better application prospect.Results:（1）The ethanol extract of Pueraria lobatae Radix（EPL）was selected as the model drug.The spray drying technology could be used as the in-and-out pore-forming method,and the fluid-bed coating technology as the surface pore-forming method.NH₄HCO₃was selected as the porogen.The preliminarily prepared porous particles were superior to the parent EPL ones in both compactibility and dissolution rate.（2）The particle porosity was increased with the amount of NH₄HCO₃ when porous EPL particles were prepared by the in-and-out pore-forming method.The results showed that there were significant differences in the fundamental and functional properties between the spray-dried and parent EPL particles.First,the irregular and dense primary EPL particles were transformed into loose,hollow,and spheroidal particles.Second,compared to parent EPL particles,porous EPL particles showed a significant improvement（1.80–7.03 times）in compactibility.Third,the design of porous particles resulted in an about 2-fold synchronous increase in the dissolution rates of all 11 peaks appearing in the characteristic fingerprint spectrum of EPL compared with parent EPL tablets.（3）The formulation of porous EPL particles was optimized by a central composite design method with two-factors and five-levels when they were prepared by the surface pore-forming method.With the maximum tensile strength and the shortest dissolution time as the optimization indexes,the optimized prescription conditions were determined as follows:the dosage of HPMC was 8.42%,and the dosage of NH₄HCO₃ was 15.00%.The various properties of optimized prescription were changed obviously compared with those of the corresponding prescription without adding NH₄HCO₃.First,the EPL particles after prepared were more porous and honeycomb-like.Second,the tensile strength of tablets produced with the optimized prescription was increased by 1.20-2.66 times compared with that of tablets produced with the corresponding prescription without adding NH₄HCO₃,indicating a significant increase in compactibility.Third,the dissolution rate of porous EPL tablets was always faster than that of parent tablets.（4）The stability of surface-porous EPL particles under the normal and accelerated conditions was investigated,and it was found that the powder properties（such as density,flowability,particle size,water content,etc.）and the tablet properties（such as compactibility,dissolution,weight difference,and brittleness）did not change significantly during the storage.The mixtures of porous EPL particles and excipients had good fluidity,and the tablet weight difference,brittleness,tensile strength and dissolution of the pressed tablets were all acceptable even under high drug loading.Conclusion:The preparation methods of porous EPL particles used in this study are simple and easy,and the products have higher porosity and larger specific surface area.The increased porosity,on the one hand,led to the increase in inter-and intra-particle bonding forces during tableting and,on the other hand,facilitated water intrusion into tablets for disintegration and dissolution.Moreover,the porous EPL particles exhibited good stability and universal applicability,indicating their good application value.Therefore,this study could be used as a reference for expanding the application of tablets in TCM and improving the quality and efficacy of some TCM tablets.