Purpose

Desvenlafaxine succinate (DSV) is a water soluble anti-depressant drug, which is rapidly absorbed after oral administration exaggerating its side effects. The current work aims to prepare controllable release DSV matrix to reduce DSV side effects related to its initial burst.

Methods

Fifteen DSV matrix formulations were prepared using different polymers, polymer/drug ratios and matrix excipients and characterized using Differential Scanning Calorimetry (DSC), infra-red (IR) spectroscopy, water uptake and in-vitro DSV release. The release kinetics were calculated to determine the drug release mechanism. Ex-vivo DSV absorption via rat intestinal mucosal cells and the calculation of the apparent permeability coefficient (Papp) were performed using everted sac technique.

Results

Maltodextrin was the best matrix excipient (F7 and F10) showing acceptable decrease in the initial burst compared to the innovator. The addition of negatively charged polymers sodium carboxy methyl cellulose (SCMC) or sodium alginate resulted in an interaction that was proved by DSC and IR findings. This interaction slowed DSV release. F10 showed an excellent absorption of more than 80% of DSV after 4 hours and the highest similarity factor with the innovator (84.7).

Conclusion

A controllable release pattern of DSV was achieved using Methocel, Maltodextrin and SCMC. The obtained results could be used as a platform to control the release of cationic water soluble drugs that suffer from side effects associated with their initial burst after oral administration.