Skip to Main Content
 

Global Search Box

 
 
 
 

Files

File List


ucin1116005486.pdf (810.49 KB)

ETD Abstract Container

Abstract Header

IMPACT OF NONIONIZABLE GLYCOL SOLUBILIZERS EXHIBITING DIFFERENT SURFACE ACTIVITIES ON INTESTINAL MEMBRANE PERMEABILITY

TRISAL, PREETI
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1116005486

Abstract Details

2005, MS, University of Cincinnati, Pharmacy : Pharmaceutical Sciences.
Oral delivery of hydrophobic drugs exhibiting poor aquous solubility represents a difficult challenge in modern drug development. Self-emulsifying drug delivery systems (SEDDS) have effectively been used to increase oral bioavailability of such compounds. Recent studies indicated that surface-active excipients incorporated into SEDDS not only affect drug solubility but may also interfere with crucial barrier properties of the intestinal mucosa limiting transepithelial transport. Nevertheless, relevant structure-function relationships have not yet been established. In this study we determined physicochemical properties of diethyleneglycol monoethyl ether (DGME, Transcutol P®) and caprylocaproyl macrogolglycerides (CCMG, Labrasol®), two excipients commonly used in SEDDS, and compared their effect on intestinal membrane permeability using the in vitro Caco-2 cell culture model. Concentration-dependent surface activity, microstructure, and phase behavior in the ternary monoolein/water/solubilizer system were used to assess physicochemical properties of DGME and CCMG, respectively. Solubilizer-induced changes in physical barrier properties of Caco-2 cell monolayers were assessed using transepithelial electrical resistance and membrane fluidity measurements. Effects on membrane permeability were determined by quantifying transepithelial transport of marker solutes that permeate the epithelial barrier via different pathways. Finally, cytotoxicity profiles of the solubilizers were estimated using MTT and LDH assays. The results from these studies suggest that both excipients exhibit surface-active properties and undergo self-aggregation beyond a specific solution concentration. For DGME, however, this limiting concentration where self-aggregation occurs is significantly greater than for CCMG. Furthermore, inclusion of this glycol ether into the binary monoolein/water system results in a broad region of isotropic liquid. This implies that DGME exhibits more hydrotrope-like properties, whereas the behavior of CCMG follows more that of a classical surfactant. Subsequent studies using the Caco-2 cell culture model demonstrated that the hydrotrope-like DGME exhibits a superior gastrointestinal safety profile over the surfactant-like CCMG. Both solubilizers were effective as permeation enhancers for solutes traversing the intestinal mucosa via passive transcellular and paracellular diffusion. In addition, inclusion of CCMG and DGME into the transport buffer inhibited functional activity of intestinal P-glycoprotein. However, it appears that DGME is less potent as permeation enhancer than CCMG, because it always required greater concentrations of the hydrotrope-like excipient to induce significant changes in intestinal permeability. For practical applications, this implies that surfactant-like excipients may serve more effectively in a dual role as solubilizer and permeation enhancer in oral SEDDS than solubilizers with hydrotrope-like properties.
Giovanni Pauletti (Advisor)
59 p.
Health Sciences, Pharmacy
solubility; excipients; paracellular; transcellular; surfactants; hydrotropes

Recommended Citations

Citations

  • TRISAL, P. (2005). IMPACT OF NONIONIZABLE GLYCOL SOLUBILIZERS EXHIBITING DIFFERENT SURFACE ACTIVITIES ON INTESTINAL MEMBRANE PERMEABILITY [Master's thesis, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1116005486

    APA Style (7th edition)

  • TRISAL, PREETI. IMPACT OF NONIONIZABLE GLYCOL SOLUBILIZERS EXHIBITING DIFFERENT SURFACE ACTIVITIES ON INTESTINAL MEMBRANE PERMEABILITY. 2005. University of Cincinnati, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1116005486.

    MLA Style (8th edition)

  • TRISAL, PREETI. "IMPACT OF NONIONIZABLE GLYCOL SOLUBILIZERS EXHIBITING DIFFERENT SURFACE ACTIVITIES ON INTESTINAL MEMBRANE PERMEABILITY." Master's thesis, University of Cincinnati, 2005. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1116005486

    Chicago Manual of Style (17th edition)

ucin1116005486
1,497
© 2005, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.