University of Illinois Urbana-Champaign

Microfluidic platforms for solid form screening of pharmaceutical parent compounds

Goyal, Sachit

Content Files
Goyal_Sachit.pdf

Permalink

https://hdl.handle.net/2142/26368

Description

Title
Microfluidic platforms for solid form screening of pharmaceutical parent compounds
Author(s)
Goyal, Sachit
Issue Date
2011-08-26T15:33:16Z
Director of Research (if dissertation) or Advisor (if thesis)
Kenis, Paul J.A.
Department of Study
Chemical & Biomolecular Engr
Discipline
Chemical Engineering
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
M.S.
Degree Level
Thesis
Date of Ingest
2011-08-26T15:33:16Z
Keyword(s)
  • Pharmaceutical crystallization
  • solid form screening
  • combinatorial screening
  • microfluidics
  • Raman spectroscopy
Abstract
Solid form screening and selection of pharmaceutical parent compounds (PCs) has been identified as a critical step in the early stages of drug development. A significant fraction of candidate PCs are rejected on account of poor physicochemical properties that affect their biopharmaceutical attributes such as bioavailability, toxicity, and stability. As a result, there is a pressing need to characterize these physicochemical properties early in the drug development process by exploring (1) all possible solid forms of a PC, and (2) the conditions favorable for formulation of these solid forms. While automated robotic systems have been developed to execute high throughput screens, these robotic tools typically require larger quantities of PC for solid form screening (~ 5 mg of material per condition) than are typically available in the initial phases of the drug development pipeline. Microfluidics has the potential to screen PCs using significantly smaller quantities of materials (~5 μg per condition), thereby enabling high throughput screening for suitable solid forms at the crucial early stages of development when only limited amounts of PC (typically 10 mg) are available. Here, we present PDMS-based microfluidic platforms that allow combinatorial mixing of PC and counter ion solutions in arrays of 24-48 sub-microliter wells enabling solid form screening by different modes of crystallization, viz. diffusive mixing, antisolvent addition, and solvent evaporation. These platforms are compatible with a wide range of solvents typically used for pharmaceutical crystallization, suffer from minimal solvent loss (enabling long-term experiments), allow improved control over solvent evaporation, and enable portability between sample loading and analysis stations. Additionally, these platforms enable on-chip characterization of the solid forms by Raman spectroscopy, circumventing the need to manually harvest crystals. The platforms were validated with several model compounds namely, naproxen, ephedrine, indomethacin, caffeine, theophylline, and tamoxifen. The microfluidic platforms developed here find immediate application in the pharmaceutical industry, as they require cheap and readily available external peripherals, such as pipettes and a vacuum source for operation.
Graduation Semester
2011-08
Permalink
http://hdl.handle.net/2142/26368
Copyright and License Information
Copyright 2011 Sachit Goyal

Owning Collections

Graduate Dissertations and Theses at Illinois PRIMARY
Graduate Theses and Dissertations at Illinois
Dissertations and Theses - Chemical and Biomolecular Engineering
Dissertations and Theses - Chemical and Biomolecular Engineering