Enhanced Solubility and Bioavailability of Dolutegravir by Solid Dispersion Method: In Vitro and In Vivo Evaluation-a Potential Approach for HIV Therapy

Being a candidate of BCS class II, dolutegravir (DTG), a recently approved antiretroviral drug, possesses solubility issues. The current research was aimed to improve the solubility of the DTG and thereby enhance its efficacy using the solid dispersion technique. In due course, the miscibility study of the drug was performed with different polymers, where Poloxamer 407 (P407) was found suitable to move forward. The solid dispersion of DTG and P407 was formulated using solvent evaporation technique with a 1:1 proportion of drug and polymer, where the solid-state characterization was performed using differential scanning calorimetry, Fourier transform infrared spectroscopy and X-ray diffraction. No physicochemical interaction was found between the DTG and P407 in the fabricated solid dispersion; however, crystalline state of the drug was changed to amorphous as evident from the X-ray diffractogram. A rapid release of DTG was observed from the solid dispersion (>95%), which is highly significant (p<0.05) as compared to pure drug (11.40%), physical mixture (20.07%) and marketed preparation of DTG (35.30%). The drug release from the formulated solid dispersion followed Weibull model kinetics. Finally, the rapid drug release from the solid dispersion formulation revealed increased C-max (14.56 mu g/mL) when compared to the physical mixture (4.12 mu g/mL) and pure drug (3.45 mu g/mL). This was further reflected by improved bioavailability of DTG (AUC: 105.99 +/- 10.07 mu g/h/mL) in the experimental Wistar rats when compared to the AUC of animals administered with physical mixture (54.45 +/- 6.58 mu g/h/mL) and pure drug (49.27 +/- 6.16 mu g/h/mL). Therefore, it could be concluded that the dissolution profile and simultaneously the bioavailability of DTG could be enhanced by means of the solid dispersion platform using the hydrophilic polymer, P407, which could be projected towards improved efficacy of the drug in HIV/AIDS.

Automated summary

The aim of this study was to enhance the solubility of dolutegravir (DTG) through solid dispersion technique, and it was found that solid dispersions prepared with P407 could significantly improve the drug release rate and bioavailability.