Skip navigation

Formation of a bile salt-drug hydrogel to predict human intestinal absorption

Formation of a bile salt-drug hydrogel to predict human intestinal absorption

Shokry, Dina S., Waters, Laura J., Parkes, Gareth M.B., Mitchell, John C. ORCID: 0000-0003-2945-3292 and Snowden, Martin J. (2018) Formation of a bile salt-drug hydrogel to predict human intestinal absorption. Journal of Pharmaceutical Sciences, 108 (1). pp. 279-287. ISSN 0022-3549 (Print), 1520-6017 (Online) (doi:https://doi.org/10.1016/j.xphs.2018.10.005)

[img] PDF (Author Accepted Manucript)
21951 MITCHELL_Formation_of a_Bile_Salt-Drug_Hydrogel_2018.pdf - Accepted Version
Restricted to Repository staff only until 13 October 2019.

Download (14MB) | Request a copy

Abstract

The unique character of bile salts to self-assemble into hydrogels in the presence of halide salts was exploited in this work to facilitate the prediction of human intestinal absorption (%HIA) for a set of 25 compounds. This was achieved by firstly incorporating each compound separately within the process of gel formation to create a series of gel-drug membranes. Scanning Electron Microscopy (SEM) analysis of the freeze-dried samples of the blank bile salt hydrogels and drug loaded bile salt hydrogels indicated a unique microstructure made of a network of intertwined fibrils. Drug-loaded sodium deoxycholate (NaDC) hydrogels were then utilised as the donor phase to study permeability using flow-through and static diffusion cells. The resulting values of the release-permeability coefficient (Kp) were then analysed, along with other molecular descriptors, for the prediction of human intestinal absorption (%HIA) using multiple linear regression (MLR). Overall, when comparing predicted values (using the systems presented in this study) with known literature values, it can be seen that both methods (i.e. using static and flow through cells) had good predictability with R2PRED. values of 79.8 % and 79.7 % respectively. This study therefore proposes a novel, accurate and precise way to predict human intestinal absorption for compounds of pharmaceutical interest using a simple in vitro permeation system. It is important to develop alternatives to the current methods used in prediction of HIA which are expensive and time consuming or include the use of animals. Therefore, the proposed method in this study being economic and time saving provides superiority over these current methods and suggests the possibility of its use as an alternate to such methods for prediction of HIA.

Item Type: Article
Uncontrolled Keywords: sodium deoxycholate, NaDC, human intestinal absorption, %HIA, hydrogels, flow-through cells, static diffusion cells, absorption, permeation
Subjects: Q Science > QC Physics
Q Science > QD Chemistry
R Medicine > RM Therapeutics. Pharmacology
Faculty / Department / Research Group: Faculty of Engineering & Science
Faculty of Engineering & Science > Department of Pharmaceutical, Chemical & Environmental Sciences
Faculty of Engineering & Science > Medway Centre for Pharmaceutical Science
Faculty of Engineering & Science > Medway Centre for Pharmaceutical Science > Pharmaceutical and Medicinal Science Research Group
Last Modified: 18 Apr 2019 11:56
Selected for GREAT 2016: None
Selected for GREAT 2017: None
Selected for GREAT 2018: None
Selected for GREAT 2019: GREAT 2
URI: http://gala.gre.ac.uk/id/eprint/21951

Actions (login required)

View Item View Item

Downloads

Downloads per month over past year

View more statistics