Electronic Theses and Dissertations

Date of Award

2017

Document Type

Dissertation

Degree Name

Ph.D. in Pharmaceutical Sciences

Department

Pharmaceutics and Drug Delivery

First Advisor

Soumyajit Majumdar

Second Advisor

Samir A. Ross

Third Advisor

Seong Bong Jo

Relational Format

dissertation/thesis

Abstract

Lipid based systems and topical ocular inserts of various drugs were developed for the intervention/treatment of posterior segment ocular complications. Indomethacin (IN) was developed into solid lipid nanoparticles (SLNs) and Nanostructured lipid carriers (NLCs). Effect of surface functionalization using chitosan (CS) on lipid nanocarriers was tested to evaluate corneal penetration. Surface modification of SLNs with CS increased ocular penetration of IN. NLCs maintained significantly higher IN concentrations in all ocular tissues tested, compared to the other formulations evaluated in vivo. Effect of surface poly (ethylene) glycol (PEG) functionalization of the NLCs on ocular disposition was studied using Ciprofloxacin (CIP) as a model drug. Transcorneal penetration of CIP from NLCs was optimum with PEG molecular weight in between 2K to 10K. In vivo ocular tissue CIP concentrations attained from the various formulations was consistent with the in vitro data obtained. Feasibility of melt-cast, topical, ocular inserts for delivery of drugs, with different physicochemical properties, to the posterior segment of the eye was studied. The model drugs tested include indomethacin (IN), ciprofloxacin hydrochloride (CIP) and prednisolone sodium phosphate (PSP). Transmembrane flux of IN, PSP and CIP were enhanced by ~3.5-folds, ~3.6-folds and ~2.9-folds, respectively, from the polymeric inserts when compared to the control formulations, post 3 h. Moreover, ocular inserts generated significantly higher drug levels in all the ocular tissues, including the retina-choroid, when compared to their control formulations. Cationic lipid nanoparticles of Natamycin (NT) were also evaluated. NT SLNs were compared with NT marketed formulation – 5% w/v ophthalmic suspension - in terms of transcorneal permeation and in vivo ocular tissue distribution. Compared to Natacyn® control, transcorneal permeability of NT was enhanced ~ 3-folds with the CLBN formulation. In vivo studies demonstrated that CLBN, at a 50-fold lower dose, was as effective as the control formulation in terms of NT delivery to the retinal tissues. Resveratrol (RES), a multi-faceted candidate was formulated into SLNs. Transcorneal flux of RES was increased ~ 1.5-folds with the SLN formulation, when compared to control formulation. The results from the all the above studies demonstrated that lipid based systems and melt-cast topical ocular inserts serve as viable platforms in the niche of ocular delivery.

Concentration/Emphasis

Emphasis: Pharmaceutics

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