Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.732896
Title: Predicting human intestinal absorption using chromatography and spectroscopy
Author: Shokry, Dina
ISNI:       0000 0004 6494 7981
Awarding Body: University of Huddersfield
Current Institution: University of Huddersfield
Date of Award: 2017
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Abstract:
New drug entities (NDE) are constantly being developed with most of them intended for oral administration. For this reason, there is a need to estimate their absorption in order to save time and money that would be lost if the drug enters the clinical stage and is then found to exhibit poor absorption. For many years, the use of animals was the most abundant method for studying pharmacokinetics to predict parameters such as intestinal absorption. However, these methods are time consuming, and expensive as well as being ethically unfavourable. As a result, developing other methods to evaluate a drug’s pharmacokinetics is crucial. The aim of this work was to develop in vitro methods for estimation of human intestinal absorption (%HIA) to replace the use of the aforementioned, less favourable methods involving the use of animals. Among the developed methods in this thesis is a unique type of chromatography known as micellar liquid chromatography (MLC) using biosurfactants such as bile salts as a mobile phase. Furthermore, studies investigated the effect of a change in the stationary phase in addition to investigating the effect of the change in temperature on the elution of the analysed compounds. It was found that R2PRED for the developed MLC methods was in the range of 43.3 % - 91.12 %. Another developed method was a spectrophotometric method based on the use of the solubilising effects of bile salts, as well as their binding to compounds. Therefore, two spectrophotometric methods were developed, a solubilisation method and a double reciprocal method, and used in the prediction of %HIA. It was found that the solubilisation method had a better predictability for %HIA than that of the double reciprocal method where R2PRED was found to be 82.32 % and 61.90 % respectively. Finally, a permeation method was developed using the ability of NaDC to form a hydrogel under specific conditions and applying the investigated drugs in an infinite dose to the prepared hydrogels. This facilitated the determination of permeability coefficients (Kp) that were then used in the prediction of %HIA using the obtained model. The two developed permeation methods were found to have close values of R2PRED for % HIA where R2PRED of the permeation method using flow through cells was found to be 79.8 % while that of the permeation method using Franz cells was found to be 79.67 %. In summary, this work reports several unique models for the in vitro prediction of human intestinal absorption, potentially removing the need for animal testing to predict %HIA.
Supervisor: Waters, Laura ; Parkes, Gareth Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.732896  DOI: Not available
Keywords: Q Science (General)
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