Oral Liquid Formulation of Etravirine for Enhanced Bioavailability

Abstract

Currently, themajority of marketed anti-AIDS are solid dosage forms and there is a need for a liquid formulation for better patient compliance especially for those who have difficulty in swallow tablets or capsules. We have developed a water soluble and stable etravirine liquid solution formulation suitable for oral administration. Oral bioavailability of the formulation was also compared with the commercial Intelence ® 100 mg Tablets.

Ligand-Based Design of Nondimethylphenyl-Diarylpyrimidines with Improved Metabolic Stability, Safety, and Oral Pharmacokinetic Profiles

“…For instance, the solubility of ETR is far below 1 μg/mL, and that of RPV is only approximately 20 ng/mL . The human oral bioavailability of ETR is still unknown because no intravenous formulation has been investigated …”

“…11 The human oral bioavailability of ETR is still unknown because no intravenous formulation has been investigated. 12 Based on the crystal structures of ETR/RPV with the reverse transcriptase (RT) enzyme, they exhibited a "U" conformation, and the dimethyl moiety limits the flexibility of the binding with the RT. 13 In 2007, structural optimizations by Johnson & Johnson Pharmaceuticals clearly demonstrated that the methyl groups could be efficiently replaced by other functionalities to decrease the cytotoxicity but do not reduce the antiviral activity.…”

Picomolar inhibitor of reverse transcriptase featuring significantly improved metabolic stability

“…The results collected in Table 6 indicated that 9g exhibited better PK profiles than 5 21 . After intravenously administrated, the maximum concentration of 9g ( C max ) reached 296 ng/mL, the half-life was 1.5 h, and the mean residence time (MRT) was 1.19 h. When 10.0 mg/kg of 9g was orally administered, the maximum concentration ( C max ) was 39.3 ng/mL at 0.83 h and the half-life was 5.21 h. It has been reported that the F value of RPV cannot be accurately determined, and the F value of ETR remains unknown 29 , 30 . Therefore, the low oral bioavailability ( F = 8.01%) requires further optimization, albeit with a slight improvement relative to compound 5 ( F = 2.39%).…”

Scalable Electrospinning Methods to Produce High Basis Weight and Uniform Drug Eluting Fibrous Biomaterials

“…These drugs are all antiretroviral agents, but have differences in water-solubility ranging from 0.011 mg/ml (National Center for Biotechnology Information, 2022b), 53.9 mg/ml (National Center for Biotechnology Information, 2022b), and 0.00397 mg/ml (John and Liang, 2014) for MVC, RAL, and ETR, respectively. These drugs also have a range of reported partition coefficients (logP) of 4.3 for MVC (National Center for Biotechnology Information, 2022a), 0.4 for RAL (National Center for Biotechnology Information, 2022b), and >5 for ETR (John and Liang, 2014). Therefore, we expect these agents to represent an interesting challenge for formulation consistency.…”