Modification of solid form of drug in oil-in-water emulsion: Effect of self-assembly of the emulsifier glycyrrhizic acid

Abstract

The encapsulation and solid form control of a hydrophobic drug in oral administration remains a persistent challenge. Here, an oil-in-water emulsion evaporation approach was developed to simultaneously control solid form and release profile of hydrophobic and amphiphilic drugs in solid dose. Hydrophobic drugs treating cardiovascular and cerebrovascular diseases (CCVD) were selected as drugs for the oil phase. A saponin with hepatoprotective effect, glycyrrhizic acid (GA), was employed as emulsifier due to its amphiphilic structure, and on the other hand, its excellent hepatoprotective effects can reduce the risk of liver disease caused by CCVD medication. By adjusting the composition of the emulsion, various GA self-assemblies were triggered including crystal, micelle and fiber. The emulsions with different GA forms at the interface subsequently act as evaporation crystallizers for CCVD-drugs. Consequently, solid form of CCVD-drugs was influenced either kinetically or thermodynamically by the GA concentration, the GA-drug miscibility and slow migration of GA fibers. Moreover, immediate and sustained release for both GA and CCVD-drugs were achieved, respectively. The emulsion evaporation approach in this work represents a strategy enabling formulation of hydrophobic and amphiphilic drugs with controlled solid forms and release profiles.