Thesis

Investigation into the use of synthetic membranes for drug diffusion in Franz cells

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Rights statement
Awarding institution
  • University of Strathclyde
Date of award
  • 2007
Thesis identifier
  • T11896
Qualification Level
Qualification Name
Department, School or Faculty
Abstract
  • Franz diffusion cells employ synthetic membranes because of membrane simplicity and supposed good reproducibility. For topical product assessment, the synthetic membrane should provide no diffusional resistance to drug diffusion, however, different synthetic membranes do show rate-limiting effects. The aims of this study were to validate and minimise errors that occur in Franz cell experiments, to examine the effect of different types of synthetic membrane on drug diffusion and to test the suitability of Franz cell experiments for drug release from a freeze-dried sodium alginate wafer and a sodium alginate gel. Franz cell experimental variables were validated using physical and visual tests, a plasticiser assay and incorporation of tonicity agents. The drug flux from a commercial gel was compared before and after validation. Thirteen types of synthetic membranes were screened using ibuprofen saturated solution. The impact of drug log P on flux was evaluated using ibuprofen (hydrophobic drug), riboflavin (hydrophilic drug) and four parabens of increasing hydrophobicity. The physical characteristics of sodium alginate gel and its lyophilised wafer were characterised by rheology, thermal analysis, microscopy and their drug release profiles compared. The coefficient of variation (CV) for drug flux was reduced from 26% to 4% (n=6) after validation of the Franz cells. The membranes were grouped into two categories, high-flux (8 - 18 mg/cm²/h) and low-flux (0.1- 3 mg/cm²/h) depending on ibuprofen flux. The riboflavin and paraben drug fluxes showed similar membrane groupings to ibuprofen. However butylparaben showed a possible drug-membrane interaction. Rheology, thermal and microscopic data showed that sodium alginate formed stable gels in ibuprofen saturated solution (pH 7.2). Using the validated Franz cells, the ibuprofen flux from sodium alginate gel and wafer were 2.55 mg/cm²/h and 1.54 mg/cm²/h respectively. This study demonstrated that the validation of Franz cells is mandatory to ensure that drug release results are solely due to the properties of the membrane and the formulation. The high flux membranes were mainly synthetic microfiltration membranes, while the low flux membranes were mostly semi-synthetic (cellulose-based) membranes. The membrane choice for quality control should be selected from the high-flux group because these membranes offer the least drug diffusional resistance. The tight CV of flux obtained demonstrated that Franz cell is a robust method for wafer and gel drug release measurement. The slower release of drug from sodium alginate wafers suggests that wafers have potential for a controlled release dressing for wound healing.
Resource Type
DOI
EThOS ID
  • uk.bl.ethos.443117
Date Created
  • 2007
Former identifier
  • 760409

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