Development of a controlled-release carrier using mesoporous cellulose beads for poorly water-soluble drugs

Aqueous solubility is one of the most critical physicochemical properties influencing oral bioavailability, as limited solubility or dissolution of drugs in the gastrointestinal tract may result in insufficient and variable absorption and low therapeutic effect. Enhancing the oral bioavailability of dissolution-impaired drug candidates therefore constitutes one of the most challenging tasks formulation scientists are faced with nowadays. Cellulose beads are a class of non-toxic biomaterial with good biocompatibility and abundant sources，and also have tunable pore diameter (meso-and macroporous) and surface properties that allow interaction with organic compounds. So it can be expected that poorly soluble drugs can be included in the pores of the cellulose particles leading to improved solubility and dissolution rate. This thesis will first focus on the evaluation of the potential of the cellulose beads to increase the apparent solubility and dissolution rate of ten poorly soluble drugs in a biorelevant medium that mimics the GI fluids. Optimize the performance of cellulose beads by adjusting the conditions in the synthesis process, such as temperature, cellulose solution concentration, nitric acid concentration, etc. Then we will develop a reservoir system based on cellulose beads with a pH-responsive coating or an enzymatic reaction coating to achieve a fixed-point or timed release of the drug using specific microenvironment changes (pH changes or microbial changes) at specific sites, and find the best polymer coating formulation by evaluating the adsorption, diffusion, drug-coating interactions, and the diffusion of water vapor over the coating on the coating prepared under different parameters.