Topical delivery of hexamidine.

Area of Science:

• Dermatology and Pharmaceutical Sciences
• Skin Penetration and Formulation Science

Background:

• Hexamidine diisethionate (HEX D) is a known biocide with emerging roles in skin homeostasis.
• Limited data exists on epidermal penetration and formulation strategies for HEX D.
• Understanding topical delivery is crucial for optimizing its efficacy.

Purpose of the Study:

• To characterize HEX D interaction with skin and develop topical formulations.
• To compare skin penetration of HEX D with its dihydrochloride salt (HEX H).
• To evaluate various solvents and enhancers for modulating skin uptake.

Main Methods:

• In vitro Franz cell permeation studies using porcine skin.
• Evaluation of neat solvents and 30 binary solvent systems.
• Investigated enhancers included glycerol, DMI, IPA, 1,2-PENT, PEG 200, PG, PGML, and Transcutol®P.

Main Results:

• Only 10 out of 30 binary systems improved skin delivery compared to neat solvents.
• Formulations with propylene glycol:propylene glycol monolaurate (PG:PGML, 50:50) showed superior topical efficacy.
• PG:PGML (50:50) resulted in >70% HEX H extraction from skin, but only 30% HEX D uptake.

Conclusions:

• Excipient effects on active delivery into skin can be unpredictable, even with minor structural differences.
• Propylene glycol monolaurate (PGML) is a promising vehicle for HEX H topical delivery.
• Further fundamental research on excipient-skin interactions is necessary for effective topical formulation development.