In vitro release of sodium diclofenac from a central core matrix tablet aimed for colonic drug delivery.
The present study was aimed at developing a novel sodium diclofenac formulation for colonic release. The proposed delivery system consisted in a polymeric matrix tablet containing a drug central core purposely designed for obtaining a time-controlled release profile characterized by an initial phase of lag-time followed by a controlled release phase, according to zero order kinetics. The spheric central core was formed by a solid dispersion of the drug into the hydrophilic polymer PEG 4000, which enabled an improvement of drug dissolution properties with respect to other carriers such as lactose. Eudragit RS100 was used as inert polymeric matrix for the core coating, mixed (50:50, w/w) with sodium chloride and Emdex as channeling agents. Tablets containing the drug central core were prepared by direct compression, without any other excipient, and tested for dissolution properties according to the USP paddle method, under pH-gradient conditions. For both series of formulations, lag times increased with decreasing the channeling agent particle size, as a consequence of the smaller pores formed by its dissolution. However, formulations containing sodium chloride always showed longer lag times than the corresponding with Emdex and were more effective in providing prolonged zero-order release periods. This was mainly attributed to the plastic deformation properties under compression shown by sodium chloride, leading to a less porous, more compact network which more strictly controlled solvent penetration and drug dissolution and release rates. By varying the sodium chloride/Eudragit w/w ratio, it was possible to suitably modulate the length of both the lag time (for achieving colonic targeting) and zero-order release phases.
D000284:Administration, Oral; D003106:Colon; D003692:Delayed-Action Preparations; D004008:Diclofenac / Q000008:administration & dosage / Q000737:chemistry*; D016503:Drug Delivery Systems; D005079:Excipients; D006863:Hydrogen-Ion Concentration; D013607:Tablets; D013997:Time Factors
D003692:Delayed-Action Preparations; D005079:Excipients; D013607:Tablets; D004008:Diclofenac