Formulation and Quality – Chemical
2019 PharmSci 360
As amorphous solid dispersions (ASDs) are more widely employed as a formulation strategy for poorly water soluble drugs, there is a pressing need to increase the drug loading in ASDs. The drug loading is typically kept low to obtain the desired drug release rates, but often results in large or even multiple dosage units, which is undesirable from a patient compliance perspective. We have identified the cause of this conundrum to be the drug loading dependent dissolution mechanism of ASDs. At low drug loadings, the dissolution rate of ASDs is polymer-controlled, while at high drug loadings, the dissolution rate is drug-controlled and considerably slower. This phenomenon is most pronounced for hydrophilic polymers, such as PVPVA and relatively hydrophobic polymers, such as HPMCAS, tend to be polymer-controlled up to higher drug loadings. Certain ternary ASD combinations also show promise as a strategy to increase the drug loading limit for polymer-controlled dissolution.