An investigation into the factors governing the degree of dissolution enhancement of solid dispersion for poorly soluble drugs

Solid dispersion (SD) formulation has attracted muchattention due to its potential in enhancing dissolutionperformances of poorly soluble active pharmaceutical ingredients(API). Recently, a review on dissolution performances of SDsclassifies the improvement into 3 categories, where 82 % of thestudies showed improved bioavailability, 8 % showed reducedbioavailability and 10 % revealed similar bioavailability ascompared to pure APIs. This indicates the inconsistent degrees ofdissolution improvement of poorly soluble APIs in SD. Althougha few factors related to the choice of carriers have been suggestedto contribute to the dissolution improvement, however, theunderlying factor determining the discrepancy in the degree ofdissolution improvement remains in vague. It is hypothesizedthat the API contributes to the degree of dissolutionimprovement of SD. Hence, the factor of amorphous solubilityadvantage of API which leads to the different degrees ofdissolution enhancement of SD is investigated in this research.Polyvinylpyrrolidone vinyl acetate (PVPVA)-based SD isprepared with three poorly soluble APIs. Physicochemicalproperties of SD were characterized using infrared spectroscopy,differential scanning calorimetry (DSC) and X-ray powderdiffraction. The dissolution efficiency of each SD was calculatedand compared to physical mixture and pure API. Theoreticalamorphous solubility advantage for each API was calculatedusing the thermal properties obtained from DSC. The calculatedvalues were found to be correlating well with the dissolutionenhancement of the respective SDs. Hence, this theoreticalapproach can be utilized as an initial screening tool of APIcandidates in SD formulation during early pharmaceuticaldevelopment