Аннотация:In situ forming implants (ISFI) based on poly(lactic-co-glycolic acid) (PLGA) are promising long-acting injectable depots for the treatment of human immunodeficiency virus-1 infection. One of the key parameters of depot formulations is the drug release rate which is critical for the development of optimal dosing regimens. The goal of this research is to investigate the most significant factors affecting the rilpivirine release rate from PLGA-based ISFI, including the influence of the polymer content and structure (i.e. molecular weights, lactide/glycolide ratios, and chemistry of the terminal group). Thus, the use of a low molecular weight PLGA reduces the burst-effect from 17.5% to 4.7% of the drug content and enables continuous release of rilpivirine over the period of 42 days. At the same time, a more hydrophobic PLGA with a lactide/glycolide ratio of 75/25 and a terminal ester group affects to a greater extent the rilpivirine release rate in the third phase of the release process, when destruction of the polymer matrix starts. The rilpivirine release profile from the implant, formed by using a 30% (w/w) solution of PLGA with a higher content of lactic acid (75:25) and a terminal ester group, is similar to the dissolution profile of rilpivirine nanocrystals (Rekambis®).