Transcutol® P/Cremophor® EL/Ethyl Oleate-Formulated Microemulsion Loaded into Hyaluronic Acid-Based Hydrogel for Improved Transdermal Delivery and Biosafety of Ibuprofen

AAPS PharmSciTech. 2019 Dec 10;21(1):22. doi: 10.1208/s12249-019-1584-8.

Abstract

In the present study, a novel transdermal delivery system was developed and its advantages were demonstrated. Ibuprofen is a commonly used anti-inflammatory, antipyretic, and analgesic drug; however, because of its short biological half-life, it must be frequently administered orally and is highly irritating to the digestive tract. To prepare a novel transdermal delivery system for ibuprofen, a microemulsion was used as a drug carrier and dispersed in a hyaluronic acid-based hydrogel (ME/Gel) to increase percutaneous drug absorption while avoiding gastrointestinal tract irritation. The prepared microemulsion had a droplet size of ~ 90 nm, and the microemulsion had good stability in the hydrogel. Rheological tests revealed that the ME/Gel is a pseudoplastic fluid with decreased viscosity and increased shear rate. It displayed a certain viscoelasticity, and the microemulsion distribution displayed minor effects on the rheological characteristics of the hydrogel system. There was no significant difference in the rheology of the ME/Gel at 25°C and 32°C (normal skin surface temperature), which is beneficial for clinical application. Drug transdermal flux was significantly higher than that of the hydrogel and commercial cream groups (p < 0.01). The 24-h cumulative drug permeation amount was 1.42-fold and 2.52-fold higher than that of the hydrogel and cream groups, respectively. By loading into the ME/Gel, the cytotoxicity of the drug to HaCaT cells was reduced. These results indicate that the prepared ME/Gel can effectively improve transdermal ibuprofen delivery and the biosafety of the drug and could therefore have applicability as a drug delivery system.

Keywords: nanocarrier; percutaneous; permeability; stratum corneum.

MeSH terms

  • Administration, Cutaneous
  • Animals
  • Drug Compounding
  • Drug Delivery Systems* / methods
  • Emulsions / chemistry
  • Ethylene Glycols / chemistry
  • Hyaluronic Acid / chemistry*
  • Hydrogels / chemistry
  • Ibuprofen / chemistry*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Oleic Acids / chemistry
  • Polyethylene Glycols / chemistry
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Emulsions
  • Ethylene Glycols
  • Hydrogels
  • Oleic Acids
  • cremophor
  • Polyethylene Glycols
  • Hyaluronic Acid
  • carbitol
  • Ibuprofen
  • ethyl oleate