Organogels, hydrogels and bigels as transdermal delivery systems for diltiazem hydrochloride

Abstract

In the present study, gel formulations of organogels, hydrogels, and oleo-hydrogel (bigels) were evaluated as transdermal drug delivery systems for diltiazem HCL (DH). Organogels were prepared using soya-bean oil (SO) as a solvent and span 60 (Sp 60), cetyl alcohol (CA) or lecithin-pluronic (PLO) as organogelators without and with different surfactants (2% w/w) namely span 80 (Sp80), tween 20 (T20) and tween 80 (T80). On the other hand, hydrogels were formulated using Hydroxypropyl-methylcellulose (HPMC) polymer and bigels were prepared by mixing organogels with HPMC hydrogels. The prepared gels were analyzed microscopically, thermally by DTA and for pH, and viscosity. The effect of gelator used, surfactant types and pH of the sink on DH release from cellophane membrane was investigated. In addition, the DH permeability across the rabbit skin was evaluated. Finally, the in vivo performance of various gel formulations was assessed based on the hypotensive effects of the drug using hypertensive albino male rat models. The microscopical analysis indicated that the solid fibers formed by gelator particles form the backbone of the organogels while bigels appeared as emulsion like. The addition of surfactants showed an increase in organogel viscosity. The thermal analysis of organogels indicated that the drug present in amorphous not in crystalline form. The release studies indicated that DH release from organogels, hydrogels and bigels could be controlled. The included surfactants decreased the DH release and permeation from organogels compared to those without surfactants using either Sp60 or CA. HPMC hydrogel and Bigels showed higher DH release and permeation rates when compared to organogels. The percent DH released in different pH values was in the following descending order: pH5.5>pH1.2>pH6.8>pH7.4. The in vivo antihypertensive activity of DH using different transdermal gels is arranged as following: hydrogels > PLO organogel > bigel> Sp 60 organogel.