The aim of this study was to engineer a DTG particle size able to provide plasma drug concentration maintenance above PA-IC-90 and, based on such drug prolonged- exposure, to evaluate the 30 days-acting injectable DTG feasibility for anti-HIV therapy. Liquidantisolvent precipitation technology was used to engineer dolutegravir particles. As a strategy for controlling variations of the habit, particle size and polymorphs of Dolutegravir, process intensification was performed using acetone, methanol, and DMSO as solvents and a temperature range from 5oCto 30oC. Physical properties of particles were characterized and in vitro drug release was measured. As a pivotal characterization, in vivo pharmacokinetic analysis was conducted in Wistar male rats. Findings revealed that crystal habit and polymorph were solvent and temperature independents. Concerning solvents, particle sizes were not markedly different. However, results suggested that the higher the temperature the higher dolutegravir particle size. Particle size ranging from 6.48 µm to 17 µm (D50) shown an accelerated release rate and 93% of the drug were released up to 12th day. Results demonstrated thatDolutegravir particles of approximately 13 µm (D50) maintained plasma drug concentration above PA- IC90 for 26 days.