Yi LiFollow

Defense Date

5-16-2019

Graduation Date

Summer 8-10-2019

Availability

Immediate Access

Submission Type

dissertation

Degree Name

PhD

Department

Pharmaceutics

School

School of Pharmacy

Committee Chair

Carl A. Anderson

Committee Member

James K. Drennen, III

Committee Member

Peter L.D. Wildfong

Committee Member

Ira S. Buckner

Committee Member

Lisa C. Rohan

Keywords

crystalline content quantification, drug-in-adhesive, transdermal patch, Near Infrared spectroscopy, Raman spectroscopy

Abstract

Drug-in-adhesive (DIA) transdermal patches are an important type of transdermal drug delivery system (TDDS). The drugs used in the DIA system are frequently present in metastable forms, such as amorphous solids or supercooled liquids. These drug states are thermodynamically unstable and tend to undergo recrystallization. Recrystallization of the active pharmaceutical ingredient can adversely affect the efficacy of transdermal products. This dissertation demonstrates a systematic approach to quantify the crystalline content of the API in DIA systems. This approach uses a novel method of preparing calibration standards and a spectroscopic method to reliably predict crystalline content in DIA patches. Spectroscopic tools, including Raman spectroscopy and near-infrared spectroscopy (NIRS), were used to determine the crystallinity of drug in transdermal patches rapidly and non-destructively with a limit of detection comparable to that of the conventional solid-state characterization techniques. Sample representativeness, analytical capability, and method suitability were integrated to form a systematic approach for crystallization quantification. The multivariate methods were validated via a fit-for-purpose approach. The results of this work demonstrated that a reliable crystalline content quantification method can be developed using vibrational spectroscopy for DIA transdermal patches. The quantitative spectroscopic methods are potential tools for supporting formulation development and physical stability evaluation of transdermal products in the pharmaceutical industry.

Language

English

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