Upgrading of dissolution and anti-hypertensive effect of Carvedilol via two combined approaches: self-emulsification and liquisolid techniques.

OBJECTIVE

The aim of the study was to design a self-emulsifying drug delivery system (SEDDS) of the anti-hypertensive Carvedilol in liquid and liquisolid forms as a way to enhance its dissolution profile and anti-hypertensive effect.

METHODS

Solubility studies of Carvedilol in various oils, surfactants and co-surfactants were conducted, followed by the construction of pseudo-ternary phase diagrams and other in vitro assessments. The selected SEDDS formulation (S1) was adsorbed onto solid powder excipients and compressed into tablets. The resulting liquisolid tablets were evaluated under British Pharmacopoeia (B.P.) specifications. Pre- and post-compression studies were performed to determine the flow properties and evaluate the liquisolid systems, followed by in vivo studies in hypertensive rats.

RESULTS

Attempts of self-emulsification, droplet size, and thermodynamic stability studies showed acceptable results for the S1 formulation containing Capryol 90, Tween 20, and Transcutol HP (10:53.3:26.2%), respectively. Pre-compression studies showed adequate flowability and compatibility of liquid and solid excipients with Carvedilol. The selected liquisolid tablet (LS7) demonstrated the best disintegration and water absorption ratio in addition to satisfactory friability and hardness. A significantly (p < .05) fast dissolution rate was observed for both SEDDS and liquisolid formulations when compared to pure drug and marketed Carvepress®. The in vivo study of LS7 formulation revealed a rapid significant (p < .01) decrease in the mean arterial pressure (MAP) of the rats (112.72 mmHg) within the first 30 min followed by a further decline (107.22 mmHg) after 1 h when compared to Carvepress®.

CONCLUSION

Self-emulsifying liquisolid tablets expressed rapid onset of action with enhanced anti-hypertensive effect of Carvedilol.