Improvements On The Key Tableting Properties Of Zingiberis Rhizoma Extracted Powders By Co-processing With Coating And Pore-forming Agents

Objective:This study aimed to improve the key tableting properties of traditional Chinese medicine（TCM）extracted powders by co-processed with coating and pore-forming agents,together with its improvement mechanism analysis,which provides a feasible strategy for increasing the drug loading of TCM tablets.Methods:Firstly,the suitable coating agent was selected based on the physical properties（powder properties,tensile strength,disintegration time,etc.）of coating agents,co-processed particles（CPs）by spray drying and fluid bed coating.Then,spray drying and fluid bed coating used as co-processing techniques,Zingiberis Rhizoma（ZR）extracted powders used as the model drug,the effects of different amounts of pore-forming agent and/or coating agent on powder and tablet properties and related mechanism analyses were investigated.On the basis,central composite design method with two-factors and five-levels was applied to optimize the formulation of CPs.Meanwhile,the applicability of the optimized formulation with conventional excipients and in other TCM extracts were studied.Results:（1）Comprehensively comparison of hydroxy propyl methyl cellulose（HPMC）,polyvinylpyrrolidone-vinyl acetate copolymer（PVPVA）and polyvinylpyrrolidone（PVP）,PVPVA was selected as the best coating agent.Preliminary results found that co-processed with coating agents by spray drying and fluid bed could effectively improve the tabletability.（2）Using spray drying as the co-processing technique,it was found in single factor investigation that as the amount of PVPVA or ammonium bicarbonate（NH₄HCO₃）increased,the tensile strength of ZR tablets also increased,while the one of the combined（NH₄HCO₃and PVPVA）CPs was further increased compared to single co-processed particles.In addition,NH₄HCO₃ helped the disintegration of the tablets.Optimization by central composite design,the optimized formulation was obtained by taking yield,tensile strength and disintegration time as indicators:the dosage of PVPVA is 10.1%,and the dosage of NH₄HCO₃ is 7.5%.（3）Using fluid bed coating as the co-processing technique,it was found that the increase in the amount of PVPVA increased the tensile strength of the tablets.The addition of NH₄HCO₃ further increased the tensile strength.On the basis of single factor experiments,central composite design method was carried out.Taking the tensile strength and disintegration time as indicators,the optimized formulation was as follows:the dosage of PVPVA is 13.4%,and the dosage of NH₄HCO₃ is 15%.（4）In the spray drying and fluid bed coating process,the mechanism of PVPVA to improve the tensile strength is as follows:because PVPVA was wrapped on the surface of ZR particles in the processing,its superior plastic deformation ability could cover up the poor properties of ZR particles.The improvement mechanism of NH₄HCO₃ was that the pores generated by its volatilization contributed to increase the binding site between particles during the tableting,thereby increasing the binding area.（5）Regardless of spray drying or fluid bed coating process,the weight difference,brittleness and disintegration time of the tablets produced by physical mixtures of optimized CPs with MCC and lactose in different proportions were all meet the relevant requirements of the pharmacopoeia,indicating its good applicability with the excipients.The other three TCM extracts were spray dried/fluid bed coated with a fixed amount of PVPVA and/or NH₄HCO₃ to explore the universal applicability of this method.Compared with parent powders,the tensile strength of single co-processing CPs was significantly improved,and the effects of combination CPs were more obvious.Conclusion:Through the method of co-processed with coating agent PVPVA and pore-forming agent NH₄HCO₃,in both spray drying and fluid bed coating processes,the tabletability of TCM extracts can be effectively improved,as well as the improvement of tablet disintegration.The combination achieves better effects than the use of each alone,and has a certain applicability,so as to provide a feasible strategy for the preparation of TCM extracts into qualified tablets with high drug loading.