Effect of Drug-Polymer Interaction on Drug Particle Size in Crystalline Solid Dispersion
OBJECTIVE To prepare crystallinesolid dispersion(CSD)with ketoconazole(KET)and sorafenib(SOR)as model drugs and poloxamer188(P188)as carrie,improve the dissolution rate of drug by reducing the drug particle size in vitro and discuss the mechanism of intermolecular interaction on drug particle size regulation.METHODS The drug-P188-CSD was prepared by rotary evaporation method.The intermolecular interaction and crystallization kinetics of drug-P188 in CSD were studied by solubility parame-ter method(SP),differential scanning calorimetry(DSC)and polarizing microscope(POM).Then the crystal domain size of drug in CSD preparation was measured by powder X-ray diffraction(PXRD).Finally,the solubilization effect of CSD preparation on insoluble drugs was evaluated by dissolution in vitro.RESULTS SP and DSC results showed that in CSD,the two model drugs interacted with P188,and the interaction between SOR and P188 was more significant.The results of POM and PXRD showed that the interaction of drug-P188 would inhibit the crystallization of P188 and reduce the drug particle size by comprehensively regulating the nucleation rate and growth rate of the drug crystal.At the same time,the stronger the interaction force,the stronger the inhibition effect on P188,and the greater the reduction of drug particle size in CSD.The results of dissolution in vitro showed that CSD preparation can effectively im-prove the dissolution of the drug.The smaller the particle size,the greater the percentage cumulative dissolution rate.CONCLUSION The stronger the interaction between drug and P188 in CSD,the greater the reduction in drug particle size,and the more significant the solubilization effect.
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