Evaluation of release enhancement of efavirenz through poloxamer solid dispersions

Abstract

Poloxamers are triblock copolymers commonly used in pharmaceutical formulation development to enhance the solubility of poorly water-soluble compounds. The present study investigated the efficiency of the hydrophilic carriers, poloxamer 188 (P188) and poloxamer 407 (P407), in preparing solid dispersions (SDs) of efavirenz (EFV), a BCS Class II antiretroviral. The SDs were prepared at a 1:3 drug:copolymer ratio (w/w) using the solvent evaporation method and characterized through solubility assays (shake-flask method) and solid-state analytical techniques, including DSC, TGA, FTIR, and XRPD. Additionally, the differences between P188 and P407 in effectively improving EFV dissolution across the physiological pH range were evaluated using a flow-through cell apparatus (USP Apparatus IV). XRPD results confirmed that both carriers stabilized EFV in its amorphous form within the SDs after 30-day stability studies. The saturation solubility of SDs prepared with P407 was nearly four times higher than those with P188 and approximately 2,000 times greater than the solubility of pure EFV (10 μg/mL). Consistent with the solubility results, dissolution testing demonstrated that P407 generally promoted higher EFV dissolution levels than P188 at all evaluated pH ranges.