Purpose <p>Basroparib, as a first-in-class tankyrase inhibitor without on-target toxicity, is a tentative BCS Class II drug with low solubility and high permeability. To improve its solubility and bioavailability, a microprecipitated bulk powder (MBP) was selected. Moreover, its formulation and preparation process were optimized to enhance its physicochemical properties, particularly drug solubility influencing the subsequent in vitro and in vivo release.</p> Methods <p>MBPs were employed to improve the therapeutic delivery of the active ingredient with polymer types, drug/polymer ratio, and anti-solvent amount. Crystallinity and the impurity profiles on the long-term stability were studied in the formulations. Additionally, in vitro and in vivo release of MBP-formulated basroparib in rats and beagle dogs were performed to support preclinical/clinical studies.</p> Results <p>MBPs were light yellowish, partially amorphous, and stable for 48 months. The stability notable change was the modest increase in water content with declined residual solvent. Overall, the parameters were within the limits and did not affect the quality of the MBPs. The optimized MBPs at a drug/polymer ratio of 1:4 and 500× anti-solvent showed a 16.1-fold increase in vitro drug release and 7.1-fold (rats) and 3.8-fold (dogs) increased in vivo exposure.</p> Conclusion <p>The optimum conditions and critical parameters were evaluated and optimized for basroparib-loaded MBPs to develop an oral dosage form with suitable in vitro and in vivo drug release that meets non-clinical requirements during early drug development. Moreover, the technique showed the feasibility readily transferred to scale up and lead to a commercial batch.</p>