Limonene GP1/PG organogel as a vehicle in transdermal delivery of haloperidol

Abstract

Penetration enhancers are a classical means for improving transdermal drug delivery (TDD). Enhancers permeate into the skin and reversibly decrease the barrier resistance. Basically, our aim is to formulate a transdermal gel containing an appropriate enhancer for a controlled drug release. Terpenes, namely limonene, linalool and cineole, in propylene glycol (PG) were first investigated in vitro for their capacity to enhance the percutaneous release of an anti-psychotic drug, haloperidol (HP). Relative to oxygenated linalool and cineole, hydrocarbon limonene was more effective as a skin enhancer; it increased human skin permeability and decreased lag time. Limonene was thus incorporated in an organogel comprised of gelator GP1 and PG. This skin-friendly gel in a transdermal patch could act as a long-acting formulation that delivers HP at a sustained percutaneous rate. The microscopic framework of the organogel is a branched network of interlocking fibres. Varying the gelator content modulates the fibre density and gel stiffness, and presents different degrees of resistance to drug diffusion on the vehicle side. Rheological and permeation studies demonstrated that an increase in gelator concentration increased gel moduli and decreased drug flux simultaneously. The rheology of the gel matrix influenced drug release rate in a manner described by several experimentally-derived correlations.