DEVELOPMENT, CHARACTERIZATION AND OPTIMIZATION OF DOLUTEGRAVIR SOLID DISPERSIONS USING PEG 6000 AND PVP K30: COMPARATIVE PROCESSING, FACTORIAL DESIGN AND TABLET DEVELOPMENT

Abstract

Background: Dolutegravir (DTG) is a potent HIV-1 integrase inhibitor with poor aqueous solubility, which can limit its dissolution and oral absorption. Objective: To develop and optimize dolutegravir solid dispersions using hydrophilic carriers for enhancement of solubility and dissolution. Methods: Solid dispersions were prepared using PEG 6000 by the melting method and PVP K30 by solvent evaporation at drug-to-carrier ratios of 1:1, 1:2, and 1:3. Corresponding physical mixtures were prepared for comparison. The formulations were evaluated for solubility, practical yield, drug content, and cumulative drug release (CDR). A 3² factorial design was applied using carrier and adsorbent concentrations as independent variables, with drug content and CDR as responses. Results: Pure dolutegravir showed a solubility of 0.0028 ± 0.015 mg/ml. Among the preliminary formulations, DSD4 showed 8.19 ± 0.034 mg/mL solubility, whereas DSD10 prepared by solvent evaporation with PVP K30 showed the highest solubility of 10.90 ± 0.035 mg/mL, with 93.76 ± 1.53% drug content and 94.86 ± 1.18% CDR. The best physical mixture (DSD16) showed comparatively lower solubility (3.72 ± 0.020 mg/mL). The factorial models were significant for drug content (p = 0.0343) and CDR (p = 0.0155), with adsorbent concentration identified as the major influencing variable. Predicted and observed responses showed close agreement during model validation. Conclusion: The developed solid-dispersion approach substantially improved dolutegravir solubility and dissolution compared with the pure drug and physical mixtures. The optimized formulation demonstrated satisfactory drug content and dissolution performance, confirming the potential of solid dispersion for improving the formulation characteristics of dolutegravir.