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Title: An investigation of the in vitro and in vivo performance of pH responsive polymer systems for ileo-colonic drug delivery
Author: Ibekwe, Valentine Chidi
ISNI:       0000 0004 2687 8268
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2007
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This study compared the in vitro and in vivo performance of four pH responsive poly(meth)acrylate polymer systems (Eudragit S organic, Eudragit S aqueous, Eudragit FS aqueous and Eudragit P4135 organic) as film coating systems for ileo-colonic drug delivery; and investigated the effect of food and in situ gastrointestinal pH on performance of Eudragit S organic polymer systems. Each polymer system was film-coated onto disintegrating prednisolone tablet cores, but difficulties were encountered during film coating with Eudragit P4135 and further work with the polymer was discontinued. Dissolution testing of coated tablets was conducted in different buffer media and pH conditions. At pH 7.4, drug release was rapid and similar in the compendial phosphate buffers, however drug release in bicarbonate buffer was markedly delayed and different for each system as follows: Eudragit S aqueous dispersion > Eudragit FS > Eudragit S organic solution. Disintegration performance of coated tablets was assessed by gamma scintigraphy in 8 fasted volunteers, with repeat administration of Eudragit FS coated tablets to assess intra-subject performance. Tablets coated with Eudragit S aqueous disintegrated prematurely in the proximal to mid-small intestine of all subjects. Tablets coated with Eudragit S (organic) and Eudragit FS disintegrated in the ileo-caecal junction, but performance of Eudragit S (organic) was variable, disintegrating in 5 out of 8 subjects; whereas Eudragit FS showed reproducible performance with disintegration in 14 out of 16 administrations. Also there was a better correlation between in vivo disintegration data and dissolution in bicarbonate buffer compared to phosphate buffer. The effect of in-situ gastrointestinal pH and food on disintegration of Eudragit S coated tablets was investigated in a 3-way cross-over study as follows: treatment 1 = coated tablet and pH capsule in fasted state (fasted); treatment 2 = coated tablet and pH capsule 30 minutes before food (pre-feed) and treatment 3 = coated tablet given after food (fed). Tablet disintegration was more rapid in the fed and pre-feed treatments. There was marked inter- and intra-individual variability in measured intestinal pH, but the pH in the mid to distal small intestine was found to be generally above 7 for most volunteers and was not markedly affected by food. Correlation of transit and disintegration data of the coated tablets with in-situ gastrointestinal pH in each subject indicates that pH is the main factor affecting dissolution, although disintegration performance was also markedly affected by transit time through the distal small intestine.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available