In vitro permeation and in vivo anti-inflammatory and analgesic properties of nanoscaled emulsions containing ibuprofen for topical delivery

Ghassan Z Abdullah¹*, Muthanna F Abdulkarim¹*, Ibrahim M Salman¹, Omar Z Ameer¹, Mun F Yam^1,2, Ahmed F Mutee¹, Mallikarjun Chitneni³, Elrashid S Mahdi¹, Mahiran Basri⁴, Munavvar A Sattar¹, Azmin M Noor^1
1School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, Malaysia; ²Faculty of Medicine and Health Science, Universiti Putra Malaysia, Selangor, Malaysia; ³School of Pharmacy and Health Sciences, International Medical University, Kuala Lumpur, Malaysia; ⁴Faculty of Science, Universiti Putra Malaysia, Selangor, Malaysia; *The first and second authors have contributed equally to this work.

Introduction: As a topical delivery system, a nanoscaled emulsion is considered a good carrier of several active ingredients that convey several side effects upon oral administration, such as nonsteroidal anti-inflammatory drugs (NSAIDs).
Objective: We investigated the in vitro permeation properties and the in vivo pharmacodynamic activities of different nanoscaled emulsions containing ibuprofen, an NSAID, as an active ingredient and newly synthesized palm olein esters (POEs) as the oil phase.
Methodology: A ratio of 25:37:38 of oil phase:aqueous phase:surfactant was used, and different additives were used for the production of a range of nanoscaled emulsions. Carbopol^® 940 dispersion neutralized by triethanolamine was employed as a rheology modifier. In some circumstances, menthol and limonene were employed at different concentrations as permeation promoters. All formulae were assessed in vitro using Franz diffusion cell fitted with full-thickness rat skin. This was followed by in vivo evaluation of the anti-inflammatory and analgesic activities of the promising formulae and comparison of the effects with that of the commercially available gel.
Results and discussion: Among all other formulae, formula G40 (Carbopol^® 940-free formula) had a superior ability in transferring ibuprofen topically compared with the reference. Carbopol^® 940 significantly decreased the amount of drug transferred from formula G41 through the skin as a result of swelling, gel formation, and reduction in drug thermodynamic activity. Nonetheless, the addition of 10% w/w of menthol and limonene successfully overcame this drawback since, relative to the reference, higher amount of ibuprofen was transferred through the skin. By contrast, these results were relatively comparable to that of formula G40. Pharmacodynamically, the G40, G45, and G47 formulae exhibited the highest anti-inflammatory and analgesic effects compared with other formulae.
Conclusion: The ingredients and the physical properties of the nanoscaled emulsions produced by using the newly synthesized POEs succeeded to deliver ibuprofen competently.

Keywords: in vivo analgesic, anti-inflammatory effects