In situ electrolyte interactions in a disk-compressed configuration systemfor up-curving and constant drug delivery

A new approach in drug delivery system design for meeting the needs that ar e associated with certain circadian variations is presented. The system is comprised of a pure compressed drug disk, which is encased by a polymeric c oat using hydroxypropylmethylcellulose or polyethylene oxide. Within the po lymeric coat, a physiologically acceptable binary electrolyte combination s uch as sodium deoxycholate and adipic acid is disposed. Through this proces s and upon exposure to dissolution media, ionic interactions occur and a te xturally variable matrix is manifested in the form of 'peripheral stiffenin g' with self-correcting boundaries as demonstrated by texture analysis stud ies. The peripheral boundaries erode and progressively shift toward the dis k-core, thus constantly reducing the diffusional pathlength with the result ant up-curving kinetics. Utilizing these mechanisms, a lag time is induced and drug is delivered over a 24-h period in one of two ways namely, in an u p-curving or constant manner for drug models theophylline and diltiazem hyd rochloride with water solubilities of 0.85% and >50% at 25 degrees C, respe ctively. It appears that for both sparingly and highly soluble drugs, sum o f the dissolution/diffusion rates, dynamics of diffusional pathlength and s ystem erosion rate control the release process. The heterogeneous nature of changes in coat thickness, stiffening dynamics and erosion rate in relatio n to disk geometry is discussed. The developed technology has potential to provide release patterns, compatible with specific chronophysiological cond itions, and overcome the absorption-limited capacity of the distal gastroin testinal tract. (C) 2000 Elsevier Science B.V. All rights reserved.