Water-swelling tablets based on hydrophobically modified poly(acrylic acid) - Effects of amphiphiles on swelling and drug release

Abstract: An important issue within the pharmaceutical world today is the increasing number of poorly soluble drugs. These often show a low bioavailability and a susceptibility to varying conditions in the intestine. Hydrophobically modified poly (acrylic acid) (HMPAA), commercially available as Pemulen TR2, has shown promising abilities to control the release of especially poorly soluble substances. In this work we have tried to further evaluate the potential of HMPAA in tablet formulations for controlled release. More importantly we have also throughout the work tried to gain more insight into the dissolution mechanisms of polymer matrix tablets in general. For this purpose we have used standardized pharmaceutical procedures and testing but also developed a new experimental setup using Nuclear Magnetic Resonance (NMR). A large part of the work has been devoted to the possible effects of adding amphiphilic compounds with respect to the presence of bile salts in the intestine. The hydrophobic model substances were released very slowly from the tablet and had linear release profiles. Large effects on the release from ionic strength and presence of surfactant in the release medium were established. This provides possible opportunities to manipulate the release from the tablets, and by adding a sufficient amount of surfactants to the tablets the effects of amphiphiles in the dissolution media could be circumvented. The developed NMR CSI technique provided an excellent complementary method for studying swelling polymer matrix tablets. It showed that the effects on the release were largely due to the (in)solubility of the polymer, where the polymer only showed limited swelling and phase separated during dissolution in pure water. In the presence of surfactant the polymer was solubilized and could swell indefinitely.