Computer-based formulation design and optimization using Hansen solubility parameters to enhance the delivery of ibuprofen through the skin

Int J Pharm. 2019 Oct 5:569:118549. doi: 10.1016/j.ijpharm.2019.118549. Epub 2019 Aug 5.


Trial-and-error approach to formulation development is long and costly. With growing time and cost pressures in the pharmaceutical industry, the need for computer-based formulation design is greater than ever. In this project, emulgels were designed and optimized using Formulating for Efficacy™ (FFE) for the topical delivery of ibuprofen. FFE helped select penetration enhancers, design and optimize emulgels and simulate skin penetration studies. pH, viscosity, spreadability, droplet size and stability of emulgels were evaluated. Franz cell studies were performed to test in vitro drug release on regenerated cellulose membrane, drug permeation in vitro on Strat-M® membrane and ex vivo on porcine ear skin, a marketed ibuprofen gel served as control. Emulgels had skin compatible pH, viscosity and spreadability comparable to a marketed emulgel, were opaque and stable at 25 °C for 6 months. Oleyl alcohol (OA), combined with either dimethyl isosorbide (DMI) or diethylene glycol monoethyl ether (DGME) provided the highest permeation in 24 h in vitro, which was significantly higher than the marketed product (p < 0.01). OA + DGME significantly outperformed OA ex vivo (p < 0.05). The computer predictions, in vitro and ex vivo penetration results correlated well. FFE was a fast, valuable and reliable tool for aiding in topical product design for ibuprofen.

Keywords: Computer-based formulation design and optimization; Emulgel; Hansen Solubility Parameters; Ibuprofen; Skin penetration enhancer; Topical.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage*
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry*
  • Chemistry, Pharmaceutical
  • Computer Simulation
  • Drug Compounding
  • Ethylene Glycols / administration & dosage
  • Ethylene Glycols / chemistry
  • Fatty Alcohols / administration & dosage
  • Fatty Alcohols / chemistry
  • Ibuprofen / administration & dosage*
  • Ibuprofen / chemistry*
  • In Vitro Techniques
  • Isosorbide / administration & dosage
  • Isosorbide / analogs & derivatives
  • Isosorbide / chemistry
  • Skin / metabolism
  • Skin Absorption*
  • Solubility
  • Swine


  • Anti-Inflammatory Agents, Non-Steroidal
  • Ethylene Glycols
  • Fatty Alcohols
  • oleyl alcohol
  • carbitol
  • 2,5-dimethylisosorbide
  • Ibuprofen
  • Isosorbide