EXPERIMENTAL SOLID DISPERSION APPROACH TO ENHANCE THE SOLUBILITY AND THERAPEUTIC PERFORMANCE OF DOLUTEGRAVIR
DOI:
https://doi.org/10.22159/ijap.2026v18i2.56835Keywords:
Dolutegravir, Soluplus®, Captisol®, Lyophilization, Solid dispersionAbstract
Objective: Dolutegravir (DTG), an HIV-1 integrase strand transfer inhibitor (INSTI), shows poor aqueous solubility (~15 µg/ml), limiting its therapeutic performance. This study aimed to enhance DTG solubility and oral bioavailability using various solid dispersion techniques.
Methods: Solid dispersions (SDs) were prepared by five methods-physical mixing, co-grinding, kneading, rota solvent evaporation, and lyophilization-using nine carriers: mannitol, PEG 4000 (polyethylene glycol 4000), PVP K90 (polyvinylpyrrolidone), HPMC E5LV (hydroxypropyl methylcellulose), Captisol®, Gelucire 44/14, Poloxamer 188, Poloxamer 407, and Soluplus® at drug-to-carrier ratios of 1:1–1:4 (w/w). Formulations were evaluated for solubility, dissolution, and in vivo pharmacokinetics in New Zealand white (NZW) rabbits using validated HPLC methods.
Results: Among 24 formulations, Lyophilization with Soluplus® and Captisol yielded the highest dissolution rates, with 89.14±1.17% and 77.14±1.63% drug release after 2 h. This marked improvement over pure DTG (14.63±0.72% release) was attributed to the effective conversion of the crystalline drug to an amorphous state and the formation of a homogeneous dispersion. Soluplus® demonstrated superior performance in enhancing DTG solubility and dissolution rate compared to Captisol. The solid dispersion formulation demonstrated superior pharmacokinetic properties compared to both the Dolutegravir and the marketed formulation. At 2 h post-administration, the mean plasma concentration for the F24 was 3236.71±461.42 ng/ml, compared to 1457.42±221.54 ng/ml for Dolutegravir and 2465.85 ±456.23 ng/ml for the marketed formulation.
Conclusion: Lyophilization with Soluplus® significantly enhanced solubility, dissolution, and oral bioavailability of DTG, providing a promising strategy for improved oral delivery. The experimental results collectively confirm that lyophilization with Soluplus® is a reproducible and scalable approach for solubility enhancement of dolutegravir.
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