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Pharmaceutically Relevant Microemulsions with Potential Topical, Ophthalmic, and Parenteral Applications

Zachar, Carrie L.

Abstract Details

2010, Master of Science in Pharmaceutical Sciences, University of Toledo, College of Pharmacy.
The purpose of this research was to formulate pharmaceutically relevant microemulsion systems using dioctyl sodium sulfosuccinate (DOSS) as the surfactant. Visually clear microemulsions were identified by titrating mixtures of DOSS and oil with water. The maximum amount of water incorporated in surfactant/oil mixtures was plotted in a ternary phase diagram. Based on the information from phase diagrams DOSS/Ethyl oleate (EO) and DOSS/Crodamol PMP (PMP) mixtures were selected for further studies. Microemulsions were characterized using polarized light microscopy, electrical conductivity, rheology, and dynamic light scattering (DLS). The effects of pH and the addition of acyclovir on the microemulsion-forming compositions were investigated. Anticipating an ophthalmic or parenteral delivery method for the formulations, an aseptic filtration method for sterilization was developed using membrane filtration. This method was validated via filtration and direct inoculation by plating on blood agar and using E. coli as the positive control. The safety of the formulations on NIH 3T3 cells was studied using a neutral red assay and validated using a Bradford protein assay. Dissolution studies were performed on microemulsions containing methylene blue to evaluate the drug release profile from the microemulsion system. A colorimetric estimation method was used to determine the amount of dye released from the formulation over a 72-hour period. DOSS/EO and DOSS/PMP mixtures were able to emulsify a maximum of 13.7% and 29.7% RO water. No birefringence was observed in the microemulsion formulations. Low electrical conductivity values of approximately 0.05 μS/cm indicated the existence of water-in-oil microemulsions. The conductivity studies demonstrated a “percolation phenomenon” in the formulations when the concentration of water exceeded a threshold value. DOSS/EO microemulsions exhibited Newtonian flow and viscosities of approximately 9 CP. Particle sizes for these DOSS/EO/water and DOSS/PMP/water systems were less than 30 nm in size (mean volume weighted diameter) as determined by DLS. The pH of the buffer influenced the total quantity of buffer that could be incorporated into microemulsion systems. Formulations filtered aseptically were free of bacteria when gram-stained and visualized under a microscope. The filtration method of sterilization was validated by the absence of microbial growth on blood agar plates over a 14-day period. All DOSS/EO microemulsion formulations showed no toxicity to 3T3 cells, except for samples with concentration of 1:15 and Wo values of 10 and 15. Acyclovir showed little effect on microemulsion formulation as similar percentages of acyclovir solution were incorporated into the DOSS/EO and DOSS/PMP mixtures as RO water. In vitro dye release studies demonstrate controlled release of the model drug over a 72-hour time period. Stable microemulsion formulations were prepared using DOSS/EO and DOSS/PMP mixtures. Development and validation of an aseptic filtration method of sterilization shows potential for these formulations to be used as parenteral or ophthalmic preparations. Successful incorporation of an anti-viral drug into the formulations containing pharmaceutically relevant components also shows potential for various drug delivery applications.
Jerry Nesamony, PhD (Advisor)
Kenneth Alexander, PhD (Committee Member)
Rose Jung, PharmD (Committee Member)
Frederick Williams, PhD (Committee Member)

Recommended Citations

Citations

  • Zachar, C. L. (2010). Pharmaceutically Relevant Microemulsions with Potential Topical, Ophthalmic, and Parenteral Applications [Master's thesis, University of Toledo]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1271273404

    APA Style (7th edition)

  • Zachar, Carrie. Pharmaceutically Relevant Microemulsions with Potential Topical, Ophthalmic, and Parenteral Applications. 2010. University of Toledo, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=toledo1271273404.

    MLA Style (8th edition)

  • Zachar, Carrie. "Pharmaceutically Relevant Microemulsions with Potential Topical, Ophthalmic, and Parenteral Applications." Master's thesis, University of Toledo, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1271273404

    Chicago Manual of Style (17th edition)