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Nose to Brain Delivery of Antiepileptic Drugs Using Nanoemulsions

Salam, Al-Maliki Shanta Taher
http://rave.ohiolink.edu/etdc/view?acc_num=mco1449771501

Abstract Details

2015, Master of Science in Pharmaceutical Science (MSP), University of Toledo, Pharmaceutical Sciences (Industrial Pharmacy).
The objective of this research work was to formulate and develop an intranasal oil-in-water nanoemulsion (NE) using spontaneous emulsification method. Based on ternary phase diagram, emulsification time, and drug solubility study, the composition ratio of surfactant:co-surfactant:oil was optimized to 2:1:1. The model antiepileptic drug chosen for loading was phenytoin. The NE preparation was evaluated for particle size, zeta potential, electrical conductivity, pH, % transmittance, polarized light microscopy, in vitro drug release studies using HPLC, sterility validation, differential scanning calorimetry (DSC), and in vitro nasal toxicity testing in bovine nasal mucosa. The nanoemulsion formulations were then subjected to stability studies for six months by storing formulations at 25±5°C and 5±3°C. The NE exhibited a clear and stable formulation with globule size less than 20 nm and neutral zeta potential. The absence of birefringence and high conductivity values indicated that the formulations were o/w NE. The pH measurements confirmed compatibility of such formulation for intranasal delivery. In vitro release study showed 100% release of the drug from NE over a period of 48 hours. The absence of any endothermic events in the phenytoin - self nanoemulsifying mixture (SNE) when analyzed in DSC conclusively indicated that phenytoin was completely solubilized in this mixture.The histopathological studies of optimized formulation did not show signs of damage on the nasal mucosa.The results of the sterility verification test demonstrated that the sterilization of the final formulation using aseptic filtration with 0.22µm filter was sufficient for rendering the formulation aseptic. The nanoemulsion was found to be stable in all the temperature conditions when particle size distribution, drug content, pH, and conductivity were taken as stability indicating parameters during the six-month study period. Based on the obtained results, the o/w phenytoin NE was found to be stable and desirable for use in intra-nasal delivery.
Jerry Nesamony (Committee Chair)
Sai Hanuman Sagar Boddu (Committee Member)
Caren L. Steinmiller (Committee Member)
Pharmaceuticals

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Citations

  • Salam, A.-M. S. T. (2015). Nose to Brain Delivery of Antiepileptic Drugs Using Nanoemulsions [Master's thesis, University of Toledo]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=mco1449771501

    APA Style (7th edition)

  • Salam, Al-Maliki. Nose to Brain Delivery of Antiepileptic Drugs Using Nanoemulsions. 2015. University of Toledo, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=mco1449771501.

    MLA Style (8th edition)

  • Salam, Al-Maliki. "Nose to Brain Delivery of Antiepileptic Drugs Using Nanoemulsions." Master's thesis, University of Toledo, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=mco1449771501

    Chicago Manual of Style (17th edition)

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This open access ETD is published by University of Toledo Health Science Campus and OhioLINK.