Ritonavir-Loaded PEG-b-PCL Polymeric Micelles: Reduced Excipient Requirements and Comparable Oral Pharmacokinetics in...

Background: Ritonavir (RTV), an HIV-1 (human immunodeficiency virus-1) protease inhibitor, has low aqueous solubility and poor oral bioavailability, requiring large amounts of excipients that result in bulky dosage forms and poor patient compliance. We aimed to develop an RTV-loaded polymeric micelle formulation with high drug loading capacity that improves aqueous solubility, reduces the excipient burden and associated excipient-related adverse effects, and remains stable after lyophilization without a cryoprotectant. Methods: RTV-loaded micelles were prepared from the amphiphilic block copolymer poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG-b-PCL) by thin-film hydration. Particle size and the polydispersity index (PDI) were measured by dynamic light scattering and encapsulation efficiency and drug content by HPLC, before and after lyophilization. The drug-to-excipient ratio was compared with the commercial product (Norvir^®), and pharmacokinetics were evaluated in male Sprague-Dawley rats after single oral administration. Results: Micelles showed a mean particle size of 25.9 ± 0.09 nm, a PDI of 0.224 ± 0.008, and an encapsulation efficiency of 98.9 ± 1.54%, with particle size and drug content retained after lyophilization and reconstitution without any cryoprotectant. Drug content reached 27.3% (w/w) versus 12.5% for the commercial product, a 2.6-fold reduction in excipients per unit dose. In rats, the micelle formulation showed pharmacokinetic parameters comparable to those of the Norvir^® suspension (C_max, 2243.9 ± 1226.4 vs. 2106.1 ± 835.9 ng/mL; AUC_last, 6695.3 ± 2162.6 vs. 8178.2 ± 2892.1 h·ng/mL; T_max, 0.9 ± 0.6 vs. 1.5 ± 0.5 h), with no significant differences. Conclusions: The PEG-b-PCL micelle achieved high RTV loading, substantially reduced excipients, and provided oral exposure comparable to the commercial product, supporting its potential as an alternative oral delivery system.