Electronic Theses and Dissertations

Date of Award

1-1-2018

Document Type

Thesis

Degree Name

M.S. in Pharmaceutical Science

Department

Pharmaceutics and Drug Delivery

First Advisor

Soumyajit Majumdar

Second Advisor

Seongbong Jo

Third Advisor

Michael A. Repka

Relational Format

dissertation/thesis

Abstract

Though nanotechnology which exploits the use of nanoparticles for therapeutic application have embarked as an emerging tool for drug delivery applications, the delivery of therapeutic molecules into deep ocular compartments has always been a challenging task. In this regard, the main objective of our current investigation was to develop and evaluate the fluocinolone acetonide (FA) loaded nanostructure lipid carrier (FA-NLC) in situ gel for improved ocular bioavailability by subconjunctival injection. FA, a corticosteroid administered for inhibiting the ocular inflammation either as intravitreal injection or as intravitreal implants. The FA-NLCs were developed by using vitamin A palmitate as one of the lipid components, to get an additional advantage in dry eye reduction which is caused by vitamin A deficiency. FA-NLCs were evaluated for physicochemical characteristics (size, polydispersity index and charge), release and stability studies. Further, in situ gel of FA-NLC was developed using gellan gum and hydroxypropyl methylcellulose as gelling agents. In situ gels were characterized for rheological behavior, in vitro release and permeability studies using corneal and scleral tissues. Furthermore, the ocular pharmacokinetic studies of in situ gel were conducted in New Zealand albino rabbits after subconjunctival injection, and compared with control formulation. Differential scanning calorimetry and Fourier-Transform Infrared Spectroscopy (FTIR) studies revealed no interaction between the drug and lipid phase and also reduction of the FA crystallinity in the NLC. FA-NLC (FN2b) sho159.1 ± 3.8 nm of size, 0.150 ± 0.05 of polydispersity index, -8.4 ± 0.4 of surface charge, 96.53 ± 2.4 of assay and 95.43 ± 2.89 % as entrapment efficiency, respectively. In situ gel prepared with gellan gum shoexcellent rheological properties, sustained drug release and significant permeability compared with control formulation. FA-NLC and in situ gel was found to be stable for 30 days at room and 4oC temperature. The in vivo studies revealed high drug concentration in the posterior section of the eye owing to high bioavailability of the drug to ocular tissues.

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