Electronic Theses and Dissertations

Date of Award

2017

Document Type

Dissertation

Degree Name

M.S. in Pharmaceutical Science

Department

Pharmaceutics and Drug Delivery

First Advisor

Sathyanarayana N. Murthy

Second Advisor

Seong B. Jo

Third Advisor

Micheal Repka

Relational Format

dissertation/thesis

Abstract

Psoriasis is a chronic skin disease that manifests as impaired epidermal differentiation. The disease is typically treated with acitretin, an effective oral cytotoxic agent. However, due to its side effects, its use is highly limited. Topical delivery of acitretin may decrease the systemic toxicity and increase the drug’s bioavailability at the pathological site. However, this approach has some limitations. The decrease in skin integrity due to psoriasis could lead to escape of drug into the systemic circulation system and consequently compromise the topical approach. Also, the high instability of acitretin in the presence of heat could limit its topical application. The aim of this work is to formulate and characterize niosomes for topical delivery of acitretin in order to decrease the drug’s systemic side effects, provide a controlled method of delivery to the pathological site, and improve the thermal stability of acitretin. To achieve this goal, acitretin niosomes were prepared using the thin film hydration technique. The niosomes were then characterized and optimized for size, entrapment efficiency, and drug release. The characterized niosomes were evaluated and investigated as a topical drug delivery system. The lead formulation displayed an optimum particle size of 471±1.15 nm with a PDI of 0.4±0.04, zeta potential of -21±0.26, entrapment efficiency of 92±2.70, and controlled drug release of 30.80±0.21 %. In vitro permeation studies across a tab-stripped epidermis showed that niosomes can control the drug permeation of compromised skin. The cumulative amount of drug permeated from niosomes was 1.87±0.09 µg/cm2, compared to 3.6±0.02 µg/cm2 with drug control and 2.4±0.08 µg/cm2 with excipient control. Also, the in vitro deposition studies showed that the amount of the drug deposited from niosomes to the epidermis after stratum corneum removal (665±0.2 ng/mg) was significantly greater than the amount of the drug in the solution and excipient control (385±0.1 and 205±0.4 ng/mg, respectively). Moreover, in vitro thermal degradation studies confirmed that the acitretin niosome formulations have a longer half-life than the drug in solution (115.75 days for samples stored at 4 °C, 60.18 days for samples stored at 24 °C, and 45.59 days for samples stored at 40 °C). In summary, the results showed that the incorporation of acitretin into niosomes for topical delivery might be a promising approach for the treatment of psoriasis.

Concentration/Emphasis

Emphasis: Pharmaceutics

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