Pharmaceutical formulations for poorly water-soluble drugs: From technology to solutions for clinical use

Thijs Rooimans

Research output: ThesisDoctoral thesis 1 (Research UU / Graduation UU)


The thesis, titled 'Pharmaceutical formulations for poorly water-soluble drugs - From technology to solutions for clinical use' explores various formulation strategies to improve the water solubility of poorly water-soluble drugs. Such drugs are often associated with poor drug absorption, which can compromise their therapeutic efficacy and necessitate innovative formulation strategies to enhance their solubility, dissolution, and ultimately, their bioavailability in the human body. While the challenges tied with poorly water-soluble drugs are longstanding, so are the established strategies employed to address them. The formulator’s toolbox, though limited, still contains overlooked possibilities to overcome these challenges. Some of these options are often, but not exclusively, linked with parenteral applications. Two of these strategies are detailed in this thesis and include mixed micelles (of bile salts and phospholipids) and lipid nanoemulsions. Additionally, it explores the more established technique of self-emulsifying drug delivery systems. The (re-)formulation of three existing poorly-water soluble drugs, known for issues related to their (bio)availability, are described using the aforementioned strategies. This includes vitamin K, propofol and idebenone, respectively. Special emphasis is giving to vitamin K. Despite our understanding of the function of vitamin K for nearly a century, the availability of various formulations since the nineteen fifties, and the global awareness for many years that current oral formulations are ineffective in preventing vitamin K deficiency bleedings (VKDBs) in infancy, progress towards a solution has been slow and is primarily driven by academic research. In thesis, for the first time, we present an oral solution which protects newborns against life-threatening bleedings. Furthermore, we provide a physicochemical explanation how the long known, but unexplained, incidence difference of VKDBs in formula-fed versus breastfed can be explained. This thesis further increases our fundamental understanding of why vitamin K deficiency bleedings still occurs, details the extemporaneous preparation of a propofol emulsion without specialized manufacturing equipment and describes how the oral bioavailability of idebenone can be improved by targeting lymphatic uptake. This thesis brings us one step closer to various technological solutions.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • Utrecht University
  • Hennink, Wim, Supervisor
  • van Nostrum, Rene, Co-supervisor
  • van Hasselt, Peter, Co-supervisor, External person
Award date7 Feb 2024
Place of PublicationUtrecht
Print ISBNs978-94-6473-332-7
Publication statusPublished - 7 Feb 2024


  • Pharmaceutical formulations
  • Poorly water-solube drugs
  • Bioavailability
  • Lipophilic drugs
  • vitamin K
  • propofol
  • idebenone
  • vitamin K deficiency bleedings
  • cholestasis
  • mixed micelles


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