ProjektportalExploration of colonic mucus as a dissolution compartment for poorly soluble drugs
Terrmin
HT25
Beskrivning
Aim: to investigate whether mucus is the main dissolution compartment for poorly soluble compounds in the colonic environment and to investigate the forms of dissolved compounds in the colonic mucus.
Background:
Colon is an important site for drug absorption, not only for extended-release products but also for poorly soluble compounds that are incompletely absorbed in the small intestine. Dissolution in colon is the crucial process for the drug to become available for absorption (1). While the amount of freely mobile fluid for drug dissolution in the colon is limited (2; 3), the colonic mucus, which is generally regarded as a diffusion barrier for drug absorption (4), contains most of bound water in the colonic lumen. The potential of mucus as a dissolution compartment has often been overlooked. Preliminary results suggest that poorly soluble compounds exhibited higher equilibrium solubility in the artificial colonic mucus solutions, and lipophilic compounds may particularly benefit more from the solubilization potential of the colonic mucus. However, further experiments are needed to confirm whether mucus is the main dissolution compartment for those compounds.
Methods:
• Porcine artificial colonic mucus (PACM) preparation based on established protocol
• Powder dissolution/permeation study in PACM in a Transwell setup, in comparison to dissolution/permeation in simulated colonic fluid
• Use HPLC to quantify drug concentration
• Use microdialysis with different molecular cutoff to reveal different forms of dissolved drugs
My task:
The task of the student is to investigate the dissolution/permeation profiles in artificial colonic mucus of poorly soluble drugs with various physicochemical properties. Powder dissolution in simulated colonic fluid will also be measured as comparisons. The student will utilize the available protocols for the Transwell study, while for the microdialysis part, the protocol will be developed together with the supervisors.
Expected results:
• Obtain dissolution/permeation profiles in artificial colonic mucus of different poorly soluble drugs.
• Improve the understanding of how poorly soluble drugs are dissolved in the colonic mucus.
Huvudområde
Läkemedelsutveckling
Ämne
Läkemedelsformulering och Molekylär galenisk farmaci
Typ
Laborativ studie
Företag
Uppsala University
Ort/Plats
Uppsala
Handledarens namn
Mingjun Wu, Christel Bergström
Handledarens e-post
mingjun.wu@uu.se
Institution
Institutionen för farmaci
Program
Apotekarprogrammet
Kurs
Fördjupningsprojekt i molekylär galenisk farmaci och läkemedelsformulering - 3FG090
Omfattning/hp
30hp
Hur många studenter kan antagas för detta projekt?
1