*3.2. Dissolution Studies*

Dissolution studies were carried out to investigate whether the salification would have improved the pharmacokinetic profile in the dissolution step which is mandatory to have absorption of the API. Theophylline alone has an amazingly good bioavailability provided by a very fast and effective dissolution. Nevertheless, we were interested in a slower dissolution profile to better control the release of the drug into the blood stream. This would help to mild the adverse effect when approaching the therapeutic dose.

Those studies demonstrated a better dissolution profile of the salt compared with the free base (Figure 6) leading to a decrease of 52% at 2 min, 54% at 6 min, and 38% at 15 min for **TS3w**. This valuable reduction might turn into an improved in-vivo performance allowing a better control of the administrated drug in terms of both therapeutic effects and adverse reactions. This is very useful in many cases, and it might even be essential when the therapeutic index is very narrow like in this case for Theophylline.

**Figure 6.** Dissolution study of Theophylline (squares) and Theophylline Squarate trihydrate (rounds).
