Nanovesicles of nitrendipine with lipid complex for transdermal delivery: pharmacokinetic and pharmacodynamic studies

Abstract

Context

Vesicular transdermal delivery can enhance the bioavailability of a drug especially affected by first-pass metabolism, e.g. nitrendipine. However effective transdermal delivery employs permeation enhancer, e.g oleic acid (OA) with ceramide 2, stearic acid, behenic acid, and cholesteryl sulfate lipid complex.

Objective

This study investigated the preparation, characterization of physicochemical properties, ex vivo permeation using human skin, pharmacokinetic parameters and antihypertensive potential in rats, of nitrendipine-loaded nanovesicles of ceramide 2, stearic acid, behenic acid and cholesteryl sulfate containing oleic acid gel (NOVG).

Materials and methods

The nanovesicles were made using film hydration method and characterized for physicochemical properties, ex vivo permeation using human skin, pharmacokinetic parameters and antihypertensive potential.

Results

Nitrendipine-loaded nanovesicles of ceramide-2 containing oleic acid (NOV-5) have shown fluxes in the range of 4.88–24.72 μg/cm²/h nitrendipine oral suspension (NOS) at equal dose. NOVG-5 has shown almost 33% reduction in blood pressure in the first hour and a further decrease of 25% in the second hour to restore the normal pressure.

Discussion

The permeation increases with increase in OA content. OA gets integrated in vesicle wall and enhances its permeability, whereas ceramide content makes sure that skin does not become damaged even after permeation.

Conclusion

NOVG-5 has shown the most favorable physicochemical properties and good permeation through skin providing good management of hypertension during crucial initial hours.

Keywords:

• Antihypertensive activity
• behenic acid
• oleic acid
• permeability
• pharmacokinetic
• stearic acid

Declaration of interest

The authors declare that there is no conflict of interests regarding the publication of this article.

Acknowledgements

The authors want to acknowledge Sederma, France (supplier Croda India) for genuine supply of Ceramide-2 and Concept Pharmaceuticals Ltd for providing nitrendipine.