Novel formulation strategies to overcome poorly water soluble compounds

  • Kelly Etherson

Student thesis: Doctoral Thesis


Drug solubility plays an important role during formulation development; it affects drug delivery and, as many new drug candidates developed have poor water solubility, it is necessary to increase their aqueous solubility for administration. The solubility increases, achieved by prodrugs or salt formation for example, are traditionally measured using the shake-flask method. This thesis investigated the advantages of the CheqSol method for phase-solubility studies. This method, using small pH changes, brings a compound close to its intrinsic solubility then alternates the system between sub- and supersaturated states. It also looked at in silico design and molecular dynamics simulations to investigate the solubilising properties of novel molecules. CheqSol studies were carried out on four compounds, two basic (propranolol HCl and atenolol) and two acidic (gliclazide and ibuprofen), in water and in the presence of HP-β-CD and two poloxamers using the Sirius T3. All three non-ionising excipients used during CheqSol assays were found to increase the solubility of the four example drugs. It was concluded that this method was suitable for phase-solubility studies using non-ionizing excipients. Molecular dynamics were carried out using Materials Studio 5.5. Five novel molecules were investigated to determine if they are predicted to increase the solubility of gliclazide and ibuprofen. The solubility enhancements were compared to HP-β-CD simulations conducted using the software. All five molecules were less effective than HP-β-CD at improving the calculated solubility parameters. Further studies would need to be conducted with excipients, with known solubility effects, for conclusions about the molecular dynamics technique to be drawn.
Date of Award7 Jan 2016
Original languageEnglish
Awarding Institution
  • University Of Strathclyde
SponsorsUniversity of Strathclyde
SupervisorGavin Halbert (Supervisor) & Moira Elliott (Supervisor)

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