Using Upsalite® as drug delivery vehicle : Increasing the solubility of poorly soluble drugs by stabilizing their amorphous state

Sammanfattning: Poor aqueous solubility is an issue not only in drug discovery and development but also for registered drug products, since poor drug solubility is often related to poor absorption (bioavailability). There are several methods available to increase the aqueous solubility and dissolution rate of pharmaceutical formulations. One new way is to incorporate the drug into mesopores, which suppresses crystallization of the drug and keeps it in an amorphous form. Consequently, the dissolution rate of the substance increases and the bioavailability might thereby be enhanced. Researchers at the division of Nanotechnology and Functional Materials at Uppsala University, led by Professor Maria Strømme, have investigated the use of Upsalite® - a mesoporous magnesium carbonate with high surface area and narrow pore size distribution - as drug delivery vehicle. Results showed that Upsalite® stabilized the amorphous state of different model substances and thereby enhanced their aqueous solubility as compared to the free (crystalline) drug. The aim of this master thesis was to incorporate four poorly soluble drug compounds into the pores of Upsalite®, followed by a comparison of the in vitro dissolution of these Upsalite®-complexes with the dissolution of corresponding commercially available drug products. The results obtained from powder X-ray diffraction showed that three out of four drug compounds were successfully loaded into Upsalite® in their amorphous state. Furthermore, results from in vitro studies in simulated intestinal fluid (pH 6.8) presented enhanced dissolution of each substance loaded into Upsalite®, as compared to their commercial equivalents. Lastly, the amorphous state of the three drug substances successfully incorporated into the pores of Upsalite®, was stable for at least one month when stored in room temperature at 75 percent relative humidity.