IngentaConnect Design and Development of Oral Oil in Water Ramipril Nanoemulsion...

Authors: Shafiq, Sheikh; Shakeel, Faiyaz; Talegaonkar, Sushma; Ahmad, Farhan J.; Khar, Roop K.; Ali, Mushir

Source: Journal of Biomedical Nanotechnology, Volume 3, Number 1, April 2007 , pp. 28-44(17)

Publisher: American Scientific Publishers

Abstract:

Ramipril, an orally active ACE inhibitor, is poorly water soluble, highly lipophilic drug with around 28-30% of variable oral absorption. Therefore, objective of our investigation was to design a thermodynamically stable and dilutable nanoemulsion formulation of Ramipril, with minimum surfactant concentration that could improve its solubility, stability, and oral bioavailability. Pseudo ternary phase diagrams were prepared by aqueous titration method. Formulations were selected at a difference of 5% w/w ofoil from the o/w nanoemulsion region of phase diagrams, which were subjected to thermodynamic stability and dispersebility tests. The composition of optimized formulation (CF3) was Sefsol 218 (20% w/w), Cremophor-EL (13.5% w/w), Carbitol (13.5% w/w), and standard buffer solution pH 5.0 (53% w/w) as oil, surfactant, cosurfactant, and aqueous phase respectively, containing 5 mg of ramipril. The formulation showed higher drug release (99.6%), lower droplet size (34.4 nm), lower polydispersity (0.037), less viscosity (119.28 cP), and infinite dilution capability. In vitro drug release of the nanoemulsion formulations was highly significant (p < 0 01) as compared to drug suspension. The relative bioavailability of ramipril nanoemulsion when compared to conventional tablet and drug suspension was 176.3% and 428.76%, respectively. The present study revealed how nanoemulsion formulation could be optimized for the delivery of hydrophobic drug in which higher drug loading, minimum surfactant concentration, and infinite dilution can be achieved without drug precipitation that will lead to higher solubility and increased bioavailability.

Design and Development of Oral Oil in Water Ramipril Nanoemulsion Formulation: In Vitro and In Vivo Assessment