pH-Sensitive mesoporous zirconium diphosphonate as drug carrier and diclofenac sodium for diseases susceptible to the circadian rhythm (rheumatic arthritis) as model drug, a lag-time combined with pH-sensitive colon-targeted drug delivery system was successfully prepared by coating lag-time films on diclofenac sodium loaded pH-sensitive mesoporous zirconium diphosphonate tablet. Based on the investigations of diclofenac sodium adsorbed onto and released from pH-sensitive mesoporous zirconium diphosphonate, a lag time of 6 h can be controlled through adjusting the thickness of lag-time film. The diclofenac sodium loaded pH-sensitive mesoporous zirconium diphosphonate tablet coated by lag-time films released no diclofenac sodium within 3 h in the simulated gastric solution, released diclofenac sodium less than 10% of gross released amount of diclofenac sodium within the first 3 h (thinked as occurring in small intestine) and slowly released diclofenac sodium more than 90% of gross released amount of diclofenac sodium within the following 46 h (considered as happening in colon) in the simulated intestinal solution. Thus, drugs for treatment of diseases susceptible to the circadian rhythm can be colon-specifically released in such dual controll of lag-time and pH-sensitive colon-targeted drug delivery system.

Key words: pH-sensitive mesoporous zirconium diphosphonate, lag time, diclofenac sodium, colon-targeted drug delivery