DICLOFENAC RELEASE FROM PHOSPHOLIPID DRUG SYSTEMS AND PERMEATION THROUGH EXCISED HUMAN STRATUM-CORNEUM

This study deals with the relationship between the colloidal structure of a topical formulation and the drug release in vitro as well as the influence of the microstructure on the stratum corneum drug permeabil ity. The nonsteroidal anti-inflammatory drug diclofenac diethylamine w as chosen as model drug. The vehicles consist of phospholipids, diclof enac diethylamine and water. Depending on the ratio of the three compo nents, these systems have various colloidal structures from liposomal dispersions via microemulsions to lamellar liquid crystals. The drug p articipates in the microstructure of the resulting systems. A dialysis membrane impregnated with silicone polymer was used for the in vitro release studies. The effective diffusion coefficient of diclofenac die thylamine changes rapidly with a phase transformation of the vehicle. Drug transport across the stratum corneum from aqueous solution and fr om vehicles with a high effective diffusion coefficient is controlled by the stratum corneum. In: contrast to this observation the flux from the phospholipid drug systems with a low effective diffusion coeffici ent is controlled by drug release from the vehicle. The diffusional re sistance inside these vehicles is higher than that in the stratum corn eum. The drug release from liposomes is too slow, so that there is no stratum corneum permeation of diclofenac diethylamine from liposomes a t all, either from large multilamellar vesicles or from small unilamel lar vesicles. Fluoromicrography of cryosections of human skin shows th at intact liposomes cannot penetrate deep into the skin. The fluoresce nce is limited to the cell layers of the stratum corneum.