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Water-in Water (W/W) Emulsion Drug Delivery Systems

Sharma, Anita
http://rave.ohiolink.edu/etdc/view?acc_num=osu1365954454

Abstract Details

2013, Doctor of Philosophy, Ohio State University, Pharmacy.
Water-in water (W/W) emulsions of aqueous biphasic polymer coacervates have very low interfacial tensions and small differences in density between the two phases. While they are inherently kinetically unstable, they cannot be stabilized using surfactants or colloidal particles. This research is aimed at enhancing their apparent stability and evaluating their potential as drug delivery systems. The viscosity of the dispersed phase and continuous phase was increased with xanthan and gellan gums, respectively, to enhance the apparent stability of the emulsions. Different methods of emulsification such as an overhead paddle stirrer, manually pumping fluids between two syringes connected by a double-hub needle, and an emulsifier twin syringe pump were evaluated in terms of the polydispersity and/or average droplet sizes of the resulting emulsions. Optical microscopy images were examined to determine the average droplet size in each case. The average droplet size obtained with the syringe pump (~ 20 µm) was larger than that obtained using the two-syringe, double-hub needle method (~15 µm). However, the syringe-pumped emulsions were relatively less polydisperse. To achieve further decreases in droplet size, the syringe-pumped emulsion was French-pressed through a Nuclepore® filter (5.0 µm). Although French-pressing decreased the average droplet size to 11-13 µm, it generated some multiple emulsion droplets. W/W emulsions creamed over a period of days; however, this did not lead to coalescence, as microscopy showed droplets persisting in apparent physical contact despite ongoing creaming. In vitro drug release studies used two model emulsion systems, i.e., one prepared with the syringe pump (Model Emulsion 1) and the other French-pressed after being syringe-pumped (Model Emulsion 2); and three different types of release models, i.e., Franz diffusion cell, dialysis sac, and a USP Apparatus 4 dialysis insert. Lidocaine was the model drug. Drug release from Model Emulsion 1 using two different sizes of diffusion cells (6.0 and 15.0 mL), and two different types of membranes, Millipore® and Nuclepore®, of different pore sizes were evaluated. The percent drug release increased with increasing pore sizes of the membranes. The 0.45 µm Millipore® membranes gave optimal release and the 15.0 mL diffusion cell produced lower overall variability in drug release. No significant differences were observed in drug release between Model Emulsions 1 and 2 in any of the release models. To focus on microdialysis-based in vivo delivery applications of the w/w emulsions, the dialysis sac model was evaluated in terms of variables affecting drug release such as temperature, pore size and surface area of the dialysis membrane, and flow rate. Linear and concentric microdialysis probes were also studied for the effects of temperature and flow rate on drug release. The w/w emulsions flowed easily through linear probes in contrast to concentric probes which had higher resistances to flow due to their tortuous pathways. Therefore, linear probes may be more appropriate to use with these emulsions. Both dialysis sacs and linear probes showed an increase in drug release with temperature and flow rate. Increases in release with temperature could be correlated with increases in the diffusion coefficients of the drug.
Sylvan Frank (Advisor)
Thomas Schmittgen (Committee Member)
Robert Lee (Committee Member)
Pharmaceuticals
Water-in water emulsions; coacervation; natural gums

Recommended Citations

Citations

  • Sharma, A. (2013). Water-in Water (W/W) Emulsion Drug Delivery Systems [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1365954454

    APA Style (7th edition)

  • Sharma, Anita. Water-in Water (W/W) Emulsion Drug Delivery Systems. 2013. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1365954454.

    MLA Style (8th edition)

  • Sharma, Anita. "Water-in Water (W/W) Emulsion Drug Delivery Systems." Doctoral dissertation, Ohio State University, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=osu1365954454

    Chicago Manual of Style (17th edition)

osu1365954454
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© 2013, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.