Design and development of nanoemulsion drug delivery system of amlodipine besilate for improvement of oral bioavailability

Abstract

Nanoemulsion (NE) of amlodipine besilate (AB) was developed by spontaneous emulsification method with the aim to enhance the solubility and oral bioavailability of AB and to achieve localized delivery of drug at target site. Pseudoternary phase diagrams were constructed to identify the NE region. The selected formulations from NE region were subjected to droplet size analysis, partitioning study and in vitro drug release. The partition coefficient was calculated and correlated with percent dissolution efficiency as a tool to predict in vitro drug release from NEs. The release of drug from NEs was significantly higher (p < 0.01) than the marketed tablet formulation. The optimal formulation contained 15% Labrafil M, 35% [Tween 80: ethanol (2:1)], and 50% by weight aqueous phase (NE3) was characterized by transmission electron microscopy (TEM) and for thermodynamic stability. The pharmacokinetics and biodistribution studies of the optimized radiolabeled formulation (^99mTc-labeled) in mice (p.o.) demonstrated a relative bioavailability of 475% against AB suspension. In almost all the tested organs, the uptake of AB from NE was significantly higher (p < 0.05) than AB suspension especially in heart with a drug targeting index of 44.1%, also confirming the efficacy of nanosized formulation at therapeutic site. A three times increase in the overall residence time of NE further signifies the advantage of NEs as drug carriers for enhancing bioavailability of AB.

Keywords::

• Amlodipine besilate
• bioavailability
• biodistribution
• nanoemulsion
• pharmacokinetics
• phase diagram
• solubility

Acknowledgement

The authors thank CDRI, Lucknow, India, for availing the size testing facility of NE and CIL, Panjab University, Chandigarh, India, for TEM analysis. They also thank Mr. Rashid Ali, INMAS, New Delhi, India, for his valuable support during in vivo studies.

Declarations of interest

The authors report no declarations of interest.