High-throughput screening of amorphous solid dispersions: a systematic approach to enhance bioaccessibility of a poorly soluble drug

Poor aqueous solubility and thereby poor and/or variable bioavailability of drug candidates is frequently overcome by developing enabling formulations such as amorphous solid dispersions (ASDs). This study proposes a systematic, miniaturized approach to evaluate the ASD developability of an active pharmaceutical ingredient (API) based on i) assessment of glass forming ability ii) assessment of the supersaturation potential of the neat API by supersaturation/permeation testing, iii) selection of an appropriate ASD carrier system using high-throughput dissolution screening of ASD films and iv) performing high-throughput dissolution/permeation testing of ASD films. The model drug candidate, RO6897779, exhibited good glass forming ability. Eight pharmaceutical polymers (CAP, Eudragit® E, Eudragit® L100, HPMC 100LV, HPMCAS-M, PVP K25, PVP VA64, and Soluplus®) were screened as ASD carriers by high-throughput dissolution testing at drug loads of 20, 30 and 40 % [w/w]. Due to poor performance of the binary systems, ternary ASDs containing Soluplus® were prepared at surfactant loads of 4, 6 and 8 % [w/w] and subsequently, high-throughput dissolution/permeation studies were conducted on selected compositions. The composition containing RO6897779 at a drug load of 20 % in Soluplus®[w/w] with the addition of 6 % [w/w] SDS yielded the best performance, but was inferior to the permeation of supersaturated neat RO6897779. Further studies should be conducted to assess the ability of this four-step, miniaturized approach to predict optimal ASD formulations over a broad range of API physicochemical properties.