Amorphous solid dispersion formulations (ASD) are increasingly being used as a formulation strategy to improve bioavailability of poorly soluble drugs. One of the limitations of ASDs, in particular for high glass transition temperature (Tg) compounds, is the drug loading threshold (termed the limit of congruency, LoC) below which rapid, complete and congruent release of drug and polymer is achieved. In this study, several ionic and non-ionic surfactants were added to atazanavir-copovidone ASDs with the main goal of increasing the limit of congruency. Atazanavir (ATZ) is a relatively high Tg compound with a LoC of 5 % drug loading (DL). Surface normalized dissolution studies revealed that addition of 5 % w/w of surfactant, sodium dodecyl sulfate (SDS) or cetrimonium bromide (CTAB), to the binary copovidone-based ASD doubled the LoC (from 5 to 10 % DL), resulting in a more than 30-fold increase in total release compared to the corresponding binary ASD. Moreover, addition of 5 % of Span®80 increased the LoC to 15 % DL. ASD Tg was found to decrease upon addition of surfactants and water sorption extent was found to increase. We speculate that surfactants act as plasticizers, which may facilitate polymer release from ASDs containing a high Tg drug, providing a possible explanation for the observed enhancement in drug release from ternary ASDs and the increase in LoC.
Keywords: Amorphous solid dispersions; Dissolution; Plasticization; Release; Surfactants.
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