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Abstract

The solubility of amprenavir was improved in the presence of vitamin E-TPGS through micelle solubilization. Vitamin E-TPGS inhibits the efflux system and enhances the permeability of amprenavir. Overall, vitamin E-TPGS enhanced the absorption flux of amprenavir by increasing its solubility and permeability. The enhancement is essential to the development of the novel soft gelatin capsule formulation of amprenavir for use in the clinic.

Validation of a differential in situ perfusion method with mesenteric blood sampling in rats for intestinal drug interaction profiling

“…In the present study, this was illustrated by assessing possible additional effects of ketoconazole and the excipient TPGS on amprenavir permeability. TPGS is a solubilizing excipient that is included in the Agenerase s formulation of the poorly water-soluble amprenavir; in addition to its solubilizing capacity, TPGS is also a potent Pgp inhibitor [20][21][22]. As amprenavir transport reached steady-state within 10-20 min (data not shown), it was possible to test three successive perfusion conditions during 120 min.…”

Novel nelfinavir mesylate loaded d -α-tocopheryl polyethylene glycol 1000 succinate micelles for enhanced pediatric anti HIV therapy: In vitro characterization and in vivo evaluation

“…More recently, it has been approved by the Food and Drug Administration (FDA) as a "pharmaceutically safe adjuvant" [23]. Due to its amphiphilic nature, it has been used as an absorption enhancer of poorly-absorbed drugs [24][25][26] related with its micelle-forming properties. Also in vitro and in vivo studies have demonstrated the inhibition of P-gp activity by TPGS resulting in an enhanced oral bioavailability of paclitaxel, cyclosporine and talinolol [25,27].…”

Preparation and Characterization of TPGS‐Colloidal Silica Microparticles for Enhancement of Solubility and Oral Bioavailability of Lercanidipine Hydrochloride

“…Furthermore, it is well known that TPGS may positively affect drug absorption by enhancing the solubility of poorly water-soluble drugs (via micellar solubilization) and the permeability of gastrointestinal epithelial cells, and by inhibiting P-glycoprotein (efflux transporter). 3,4 In fact, TPGS acts as a solubilizing excipient as well as a Pglycoprotein inhibitor for poorly absorbed drugs. Previously, it was reported that the bioavailability (AUC) of talinolol in healthy volunteers increased by 39% with coadministration of TPGS, via its inhibition of the P- glycoprotein activity.…”

“…1,2 TPGS has been widely used in the pharmaceutical industry as an emulsifier, solubilizer, stabilizer, and absorption enhancer by inhibition of P-glycoprotein. 3,4 Recently, the function and applications of TPGS in drug delivery were extensively reviewed by Zhang et al 5,6 Several studies have reported that TPGS improves the solubility and oral absorption of cyclosporine, paclitaxel, and sirolimus through solid dispersion techniques and micelle formulations. [7][8][9] However, because of TPGS 1000 low melting point, it is very sticky at room temperature, which results in solid dispersion preparation of it to be waxy and poor-flow.…”