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Enabling solid lipid nanoparticle drug delivery technology by investigating improved production techniques

Triplett, Michael David, II
http://rave.ohiolink.edu/etdc/view?acc_num=osu1101830018

Abstract Details

2004, Doctor of Philosophy, Ohio State University, Chemical Engineering.
Industry estimates suggest that approximately 40% of lipophilic drug candidates fail due to solubility and formulation stability issues, prompting significant research activity in advanced lipophile delivery technologies. Solid lipid nanoparticle technology represents a promising new approach to lipophile drug delivery. Despite numerous research studies demonstrating improved therapeutic drug profiles, the commercialization of solid lipid nanoparticle technology remains limited. Physical instability and drug burst release have undermined performance while commercialization has been impeded by the lack of a large-scale, economically efficient production process. Research has been conducted with the objective of advancing solid lipid nanoparticle production technology. Formulation and process effects on solid lipid nanoparticle size distribution, stability, drug loading, and drug release have been investigated, culminating in a novel solid lipid nanoparticle synthesis approach based on electrohydrodynamic aerosolization. Utilizing a high-shear homogenization technique, effects of mixing speed, mixing time, and material concentrations were investigated using an experimental design approach. Experimentation showed stearic acid as the optimal lipid, sodium taurocholate as optimal cosurfactant, a 3:1 lecithin to sodium taurocholate ratio provided optimum performance, and mixing time and speed were inversely related to nanoparticle size and polydispersity. Beta-carotene was successfully incorporated into stearic acid nanoparticles. Beta-carotene entrapment efficiency was shown to have a maximum of 80 % with a mean of 40 %. Entrapment efficiency decreased with increasing Beta-carotene concentration. Beta-carotene was retained in the nanoparticles for one month, the maximum time period examined. A maximum Beta-carotene concentration of 0.39 mg/ml was obtained in the nanoparticle suspension. An electrohydrodynamic aerosolization device was designed and constructed for making solid lipid nanoparticles. Using water, sodium dodecyl sulfate, and potassium chloride, stable cone-jets were produced at voltages applied to the stainless steel needle ranging from -1.4 kV to - 6.2 kV. When commercial vegetable oil was substituted for water, stable cone-jets were produced at voltages from -1.6 kV to - 5.7 kV. The use of electrohydrodynamic aerosolization to produce lipid nanoparticles was demonstrated. Using oleic acid, Pluronic F-68, and potassium chloride, particles possessing number distribution median diameters of 82 nm, 180 nm, and 210 nm were produced. Future electrohydrodynamic aerosolization device recommendations were included.
James Rathman (Advisor)
188 p.
Solid lipid nanoparticle; electrohydrodynamic aerosolization; electrospray; drug delivery; poorly-soluble drugs; emulsion; nanoparticle; aerosol

Recommended Citations

Citations

  • Triplett, II, M. D. (2004). Enabling solid lipid nanoparticle drug delivery technology by investigating improved production techniques [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1101830018

    APA Style (7th edition)

  • Triplett, II, Michael. Enabling solid lipid nanoparticle drug delivery technology by investigating improved production techniques. 2004. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1101830018.

    MLA Style (8th edition)

  • Triplett, II, Michael. "Enabling solid lipid nanoparticle drug delivery technology by investigating improved production techniques." Doctoral dissertation, Ohio State University, 2004. http://rave.ohiolink.edu/etdc/view?acc_num=osu1101830018

    Chicago Manual of Style (17th edition)

osu1101830018
11,216
© 2004, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.