Electronic Theses and Dissertations

Date of Award


Document Type


Degree Name

Ph.D. in Pharmaceutical Sciences


Pharmaceutics and Drug Delivery

First Advisor

S. Narasimha Murthy

Second Advisor

Seongbong Jo

Third Advisor

N. P. Dhammika Nanayakkara

Relational Format



Skin forms a formidable barrier protecting the human body from external environmental rigors and excessive loss of water; maintaining equilibrium. The barrier properties of the skin can be attributed to its unique macromolecular organization and morphology. As a route for drug administration, skin presents a large surface area and can be used for both systemic and localized targeted drug delivery applications offering several advantages over conventional drug therapy; avoidance of first pass metabolism, patient compliance, sustained or controlled delivery for an extended period, to name a few. However, the organized structure of the skin, since intended to prevent entry of adverse chemicals, poses a formidable challenge to molecular transport. From a drug delivery perspective, skin is different from GIT in anatomy and functionality, the former being more permeable to drug molecules. Through various peer revieresearch on the drug transport kinetics through skin, it has been realized that the primary barrier to cutaneous drug transport resides in the Stratum Corneum (SC), the uppermost layer of the skin. The 15-20 μm thick lipophilic, torturous morphology of the SC resembles a brick and mortar structure and imposes a limitation on percutaneous drug transport with only a few molecules having the prerequisite physicochemical characteristics to permeate the intact SC. Thus, drug penetration and subsequent diffusion across the SC is a passive process leading to constraints on the amount of drug that is deliverable to achieve the desired therapeutic effect. To increase the number of candidates for cutaneous delivery and to attain appropriate dose levels requires application of certain enhancement strategies. These approaches employ different mechanisms; (i) an external driving force by iontophoresis (ii) reversible modulation of the SC barrier function by chemical penetration enhancers (iii) creating “easy access” transport channels by microneedles. Nevertheless, a thorough understanding of the molecular transport process across the skin is requisite before formulation strategies could be employed to deliver drugs across the skin in a therapeutically pertinent time-frame. The research presented in this dissertation addresses the knowledge gap that pertains to percutaneous drug absorption by investigating the transport of drug molecules into the skin after a short-term exposure (5 minutes) to aqueous and ethanolic drug solution. Further, the research demonstrates the effect of chemical & physical enhancement approaches: chemical penetration enhancers and microneedles on skin permeability to drug molecules.



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