In situ electrolyte interactions in a disk-compressed configuration system for up-curving and constant drug delivery.
A new approach in drug delivery system design for meeting the needs that are associated with certain circadian variations is presented. The system is comprised of a pure compressed drug disk, which is encased by a polymeric coat using hydroxypropylmethylcellulose or polyethylene oxide. Within the polymeric coat, a physiologically acceptable binary electrolyte combination such as sodium deoxycholate and adipic acid is disposed. Through this process and upon exposure to dissolution media, ionic interactions occur and a texturally variable matrix is manifested in the form of peripheral stiffening' with self-correcting boundaries as demonstrated by texture analysis studies. The peripheral boundaries erode and progressively shift toward the disk-core, thus constantly reducing the diffusional pathlength with the resultant 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 up-curving or constant manner for drug models theophylline and diltiazem hydrochloride with water solubilities of 0.85% and > 50% at 25 degrees C, respectively. It appears that for both sparingly and highly soluble drugs, sum of the dissolution/diffusion rates, dynamics of diffusional pathlength and system erosion rate control the release process. The heterogeneous nature of changes in coat thickness, stiffening dynamics and erosion rate in relation to disk geometry is discussed. The developed technology has potential to provide release patterns, compatible with specific chronophysiological conditions, and overcome the absorption-limited capacity of the distal gastrointestinal tract
Pillay
V
V
Department of Pharmaceutical Sciences, School of Pharmacy, Temple University, 3307N Broad Street, Philadelphia, PA 19140, USA.
Fassihi
R
R
D004110:Diltiazem / Q000008:administration & dosage / Q000737:chemistry; D016503:Drug Delivery Systems; D004573:Electrolytes; D006863:Hydrogen-Ion Concentration; D065347:Hypromellose Derivatives; D007700:Kinetics; D008747:Methylcellulose / Q000031:analogs & derivatives; D008970:Molecular Weight; D011092:Polyethylene Glycols; D012995:Solubility; D013608:Tablets, Enteric-Coated; D013806:Theophylline / Q000008:administration & dosage / Q000737:chemistry
D004573:Electrolytes; D013608:Tablets, Enteric-Coated; D065347:Hypromellose Derivatives; D011092:Polyethylene Glycols; D008747:Methylcellulose; D013806:Theophylline; D004110:Diltiazem