The Application Of AFFINISOL^TM HPMC HME In HME Technology

Objective: The purpose of this paper is to study the application of AffinisolTM HPMC HME in hot melt extrusion technology.The physical properties and extrusion characteristics of AffinisolTM HPMC HME excipients were evaluated by studying how formulation compositions and process parameters affect the drug dissolution profiles.Also the stability research of the solid dispersions prepared with different extrusion excipients were investigated to get better understanding of their performance difference.It is expected that this study would provide useful information for the future application of AffinisolTM HPMC HME in hot melt extrusion.Method: In this paper,a water-insoluble drug irbesartan for the treatment of hypertension,was selected as the model drug for tabletting through hot melt extrusion technology.The dissolution test was utilized to evaluate the difference among AffinisolTM HPMC HME and other commonly used hot melt extrusion carriers(VA 64,Soluplus,HPMC E5)in hot melt extrusion applications.First,the effects of different preparation methods and different extrusion carriers(AffinisolTM HPMC HME 15 LV,AffinisolTM HPMC HME 100 LV,AffinisolTM HPMC HME K4 M,VA64,Soluplus,HPMC E5)on tablet drug release were analyzed.Then,the relationship between the amount of carrier(AffinisolTM HPMC HME 15 LV,AffinisolTM HPMC HME 100LV)and plasticizer(P 188,PEG 6000,ATO)was investigated by single factor experiment.Furthermore,the relationships among process parameters,torque and pressure changes were studied.Finally,in the stability study,the hygroscopicity difference among Affinisol HPMC HME,commonly used HME excipients and traditional HPMCs was investigated.The stability of the extrudate and formulation were evaluated by applying differential scanning calorimetry(DSC)and in vitro release in different storage conditions.Result: Through the study of this paper,it was found that the irbesartan tablets prepared by physical mixing and wet granulation release 40% and 50% respectively at 45 min.The irbesartan tablets prepared by hot melt extrusion method released 90% at 10 min,which indicated that the solid dispersion prepared by hot melt extrusion method had better solubilization effect.The release of irbesartan tablets prepared by different extruded carriers was as follows: The release of irbesartan tablets prepared by HPMC E5 and Affinisol HPMC HME K4 M was 26% and 40%,respectively.The release speed rank is AFF 15LV> VA 64> AFF100LV> Soluplus.Compared with the traditional HPMC,AffinisolTM HPMC HME carrier solubilization effect is significant.In the study of formulation composition and drug release,the irbesartan tablets prepared with AffinisolTM HPMC HME 15 LV and 100 LV as carriers could reach more than 85% release at 15 min,and the solubilization effect was good.With the increase of plasticizer,the drug release slows down,the possible reason could be that the plasticizer is more likely to form micelles that cause the release to slow down.The release results of the solid dispersions prepared by three types of plasticizers(P 188> PEG 6000> ATO)were as follows: 99.23%,87.62% and 71.03%,respectively.From the research,it was found that with the increase of the extrusion temperature,the torque and pressure of AffinisolTM HPMC HME decrease slowly,and reach 30-50% and 30-50 pa respectively.While the traditional HME excipients VA 64 and Soluplus are more sensitive to extrusion temperature and rotation speed during the process of extrusion,and decrease to less than 10% and 10 pa.Moreover for the same formulation containing AFF 15 LV or AFF 100 LV at the same extrusion speed,it was found that the higher the extrusion temperature,the faster the drug release.For the same extrusion temperature,the drug release is increased with the increase of the extrusion speed in the beginning,and then decrease.In the stability study,the hygroscopicity of AffinisolTM HPMC HME was significantly lower than that of VA 64 and HPMC E5.In the accelerated stability test,it was found that the DSC profiles of the extrudate prepared with AffinisolTM HPMC HME stay unchanged,and the extrudate prepared with VA 64 showed unstable profile.after 3 months.The dissolution profile of the formulation prepared with AffinisolTM HPMC HME didn't change significantly at 3 month,and the drug release rate of the tablet prepared with VA 64 as the extruded decreased.Conclusion: AffinisolTM HPMC HME shows better solubilization effect,superior thermal processing capability and more stable dissolution profile,compared to the traditional extrusion excipients.Moreover there are different grades of AffinisolTM HPMC HME available to choose for different drug release needs.The research of the thesis can provide a reference for the selection of hot melt extrusion excipients.