Development and bioavailability assessment of ramipril nanoemulsion formulation

Eur J Pharm Biopharm. 2007 May;66(2):227-43. doi: 10.1016/j.ejpb.2006.10.014. Epub 2006 Oct 24.

Abstract

The 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. Formulations were taken from the o/w nanoemulsion region of phase diagrams, which were subjected to thermodynamic stability and dispersibility tests. The composition of optimized formulation was Sefsol 218 (20% w/w), Tween 80 (18% w/w), Carbitol (18% w/w) and standard buffer solution pH 5 (44% w/w) as oil, surfactant, cosurfactant and aqueous phase, respectively, containing 5 mg of ramipril showing drug release (95%), droplet size (80.9 nm), polydispersity (0.271), viscosity (10.68 cP), and infinite dilution capability. In vitro drug release of the nanoemulsion formulations was highly significant (p<0.01) as compared to marketed capsule formulation and drug suspension. The relative bioavailability of ramipril nanoemulsion to that of conventional capsule form was found to be 229.62% whereas to that of drug suspension was 539.49%. The present study revealed that ramipril nanoemulsion could be used as a liquid formulation for pediatric and geriatric patients and can be formulated as self-nanoemulsifying drug delivery system (SNEDDS) as a unit dosage form.

Publication types

  • Comparative Study

MeSH terms

  • Administration, Oral
  • Angiotensin-Converting Enzyme Inhibitors / administration & dosage
  • Angiotensin-Converting Enzyme Inhibitors / blood
  • Angiotensin-Converting Enzyme Inhibitors / chemistry*
  • Angiotensin-Converting Enzyme Inhibitors / pharmacokinetics
  • Animals
  • Biological Availability
  • Buffers
  • Capsules
  • Chemistry, Pharmaceutical
  • Drug Compounding
  • Drug Stability
  • Emulsions*
  • Ethylene Glycols / chemistry
  • Hydrogen-Ion Concentration
  • Male
  • Models, Biological
  • Nanoparticles*
  • Oils / chemistry*
  • Pharmaceutical Solutions
  • Phase Transition
  • Polysorbates / chemistry
  • Ramipril / administration & dosage
  • Ramipril / blood
  • Ramipril / chemistry*
  • Ramipril / pharmacokinetics
  • Rats
  • Rats, Wistar
  • Solubility
  • Surface-Active Agents / chemistry
  • Technology, Pharmaceutical / methods
  • Thermodynamics
  • Viscosity

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Buffers
  • Capsules
  • Emulsions
  • Ethylene Glycols
  • Oils
  • Pharmaceutical Solutions
  • Polysorbates
  • Surface-Active Agents
  • carbitol
  • Ramipril