Drug Delivery and Translational Research - Featured Article: January 2023
Read the featured article from the January 2023 issue! (this opens in a new tab)
The therapeutic potential of atazanavir (ATZ), a highly selective inhibitor of human immunodeficiency virus (HIV-1), has been largely limited due to its low oral bioavailability. The current study describes systemic development and evaluation of hydroxypropyl methylcellulose acetate succinate (HPMC-AS)-based supersaturable preconcentrate isotropic mixture (SP-IM) that enhances intestinal lymphatic transport and thus oral bioavailability of ATZ. A D-optimal mixture design was employed to optimize the composition of the critical quality attributes of the IM. In silico analysis and in vitro supersaturation test revealed HPMC-AS as a best suited polymeric precipitation inhibitor for formulating ATZ-loaded SP-IM (ATZ-SP-IM). ATZ-SP-IM exhibited superior dissolution in 0.025 N HCl and pH 6.8 over pure drug. Ex vivo permeation and in vivo pharmacokinetic (PK) studies showed that ATZ-SP-IM provided enhanced permeation and drug absorption via lymphatic transport. Further, the PK performance of ATZ-SP-IM was not affected in presence of H2 receptor antagonist. The results collectively shows that ATZ-SP-IM can significantly improve the biopharmaceutical attributes of ATZ, thereby laying a foundation of further research on the new dosage form of ATZ.