Mechanical agitation can increase the rate at which substances dissolve, improving drug bioavailability. While agitation is commonly used in vitro, adapting it for in vivo applications presents challenges. The document discusses developing remote stirring devices that can be simply applied and removed to agitate substances within the body, as well as other preliminary approaches like externally applying force, but notes more work is needed to realize agitation's potential for improving drug delivery in vivo.

1. In Vivo Agitation for Increased Drug Bioavailability

2. Agitation: Theory Substances dissolve more quickly when stirred.

3. Agitation: devices Many devices are commercially available handle Stirring blade “Recent advances in mechanical agitation technology”, Harrisson, S.; to be submitted to Nature

4. Agitation: in vitro medicinal applications Agitation was known to Shakespeare to improve the efficacy of medicinal preparations* * Shakespeare, W. Macbeth, 1597 Heating apparatus But current methods are unsuited to in vivo applications

5. Adaptation to in vivo  Simple concept  Some problems in clinical trials

6. Remote stirring Simple application and removal Remote application of stirring force (and optional heating)

7. Alternate approaches Externally applied mechanical force Murine model Shaker table Difficult to replicate in human models Promising animal studies

8. Future work ?? Exploit recent technological advances in mixer design