Fast-dissolving sublingual solid dispersion and cyclodextrin complex increase the absorption of perphenazine in...

Area of Science:

• Pharmacokinetics and Drug Delivery
• Pharmaceutical Sciences

Background:

• Perphenazine exhibits poor water solubility and significant first-pass metabolism, limiting its oral bioavailability.
• Effective drug delivery strategies are crucial for improving the therapeutic efficacy of poorly soluble drugs.

Purpose of the Study:

• To investigate sublingual administration as a route to enhance perphenazine absorption.
• To evaluate the utility of macrogol 8000 solid dispersion and beta-cyclodextrin (β-CyD) complexation for improving perphenazine bioavailability.

Main Methods:

• Perphenazine absorption was assessed in rabbits following sublingual administration of a perphenazine/macrogol solid dispersion, a perphenazine/β-CyD complex, and micronized perphenazine.
• Comparative peroral administration of an aqueous perphenazine solution and intravenous administration were also performed.

Main Results:

• Sublingual administration yielded significantly higher perphenazine bioavailability compared to peroral administration.
• Perphenazine/macrogol solid dispersion (53%), perphenazine/β-CyD complex (41%), and micronized perphenazine (64%) showed improved absorption relative to intravenous administration.
• These improvements are attributed to avoidance of first-pass metabolism, efficient sublingual absorption, and rapid drug dissolution.

Conclusions:

• Sublingual administration, particularly with solid dispersions or cyclodextrin complexes, can successfully enhance perphenazine absorption.
• Micronization is also an effective strategy for improving sublingual perphenazine bioavailability.
• This study is among the first to demonstrate the in vivo efficacy of sublingual solid dispersions.