Preparation Of Lacidipine Solid Dispersion And Its Pharmacokinetic Study In Rats

Objective:The water solubility of drugs is an important factor affecting the bioavailability of poorly soluble drugs.As a promising solubilization technology,solid dispersion can significantly improve the apparent solubility and dissolution of poorly soluble drugs,thereby improving the bioavailability of poorly soluble drugs.In this paper,taking BCSⅡdrugs as model drugs,by screening hydrophilic polymers and surfactants,a ternary solid dispersion composed of BCSⅡdrugs,hydrophilic polymers,and surfactants was constructed for improving difficult-to-improve ternary solid dispersions.Dissolution and bioavailability of soluble drugs.Methods:In this paper,lacidipine（LCDP）was used as a model drug,and the hydrophilic polymer Soluplus^?and the surfactant Gelucire^?44/14were used as carriers to screen the formulations,and LCDP ternary solid dispersions were prepared by spray drying.The existence of LCDP in solid dispersion was detected by DSC and PXRD;the appearance of LCDP ternary solid dispersion was observed by SEM;the interaction between raw and auxiliary materials in LCDP ternary solid dispersion was explored by FTIR.At the same time,the dissolution characteristics of LCDP ternary solid dispersions in different dissolution media were investigated.Under the conditions of strong light,high humidity and high temperature,the stability of LCDP ternary solid dispersion was investigated,and the pharmacokinetic test of LCDP ternary solid dispersion was carried out in rats.Results:Using the equilibrium solubility of LCDP in surfactants as an index,the surfactants were screened.Taking the precipitation inhibition ability of LCDP as an indicator,the screening parameters were selected by examining the types of hydrophilic polymers,the mass ratio of Soluplus^?to LCDP,the mass ratio of Soluplus^?to Gelucire^?44/14,and the mass ratio of carrier to LCDP.The prescription of LCDP ternary solid dispersion was determined,and the prescription of LCDP ternary solid dispersion was determined as LCDP:Soluplus^?:Gelucire^?44/14=1:6:1,and LCDP ternary solid dispersion was successfully prepared by spray drying method body.DSC and PXRD results show that LCDP is amorphous in LCDP ternary solid dispersion.SEM results show that LCDP ternary solid dispersions are regular spherical particles with a particle size in the range of 40-60μm.FTIR spectrum analysis showed that there was intermolecular hydrogen bond interaction between LCDP and excipients.In the in vitro dissolution experiment,when p H=4.50 acetate buffer and 1%Tween 20 solution were used as dissolution media,the cumulative dissolution rates of LCDP ternary solid dispersion at 240 min were 97.58%and 97.73%,respectively,higher than Cumulative dissolution of drug substance LCDP and binary solid dispersion.However,when p H=6.80 phosphate buffer and 0.1%Tween 20 solution were used as the dissolution medium,the cumulative dissolution rates of LCDP ternary solid dispersion at 240 min were 79.75%and 100.54%,respectively,which were dissolved with LCDP binary solid dispersion.There was no significant difference in the degree of dissolution,which was higher than the cumulative dissolution rate of the API LCDP.In the stability test,after being placed under strong light irradiation for 10days,the LCDP ternary solid dispersion changed from the original white powder to a yellow powder,and the labeled amount of the drug decreased from 95.29%to 4.44%;placed under high temperature conditions for 10days,the appearance of the drug and the labeled amount have almost no change;after 10 days under high humidity conditions,the labeled amount of the drug decreased,and the powder appeared agglomerated due to moisture absorption.When placed under high temperature and high humidity for 10 days,the dissolution rate of LCDP in LCDP ternary solid dispersion decreased.SD rat pharmacokinetic test results showed that the Tmax of LCDP API,LCDP binary solid dispersion(without Gelucire^?44/14 component)and LCDP ternary solid dispersion were 4 h,1 h and 2 h,respectively.,indicating that LCDP binary solid dispersion and LCDP ternary solid dispersion can accelerate the absorption rate of LCDP in rats.Both AUC_lastand AUC_all of LCDP ternary solid dispersions were higher than those of APIs,indicating that LCDP ternary solid dispersions could improve the bioavailability of LCDP in rats.Conclusion:Through a series of single factor screening experiments,the final formulation of LCDP ternary solid dispersion is LCDP:Soluplus^?:Gelucire^?44/14=1:6:1,and LCDP ternary solid was successfully prepared by spray drying method.Dispersion particles.LCDP exists in an amorphous state in LCDP ternary solid dispersion,the particles are regular spherical structure,and there is intermolecular interaction between LCDP and excipients(Soluplus^?and Gelucire^?44/14);in in vitro dissolution experiments,the LCDP ternary solid dispersion improves the dissolution rate of LCDP.In the pharmacokinetic experiment in rats,the Tmax of LCDP ternary solid dispersion is advanced and Cmax is increased,which can improve the bioavailability of LCDP in rats.It shows that the composite carrier composed of Soluplus^?and Gelucire^?44/14 has potential application value in promoting the dissolution and bioavailability of poorly soluble drugs.There are 24 Figures,18 Tables,56 References...