IN-VIVO AND IN-VITRO DICLOFENAC SODIUM EVALUATION AFTER RECTAL APPLICATION OF SOFT GELATIN CAPSULES ENABLING APPLICATION INDUCED TRANSFORMATION (AIT) INTO A SEMISOLID SYSTEM OF LIQUID-CRYSTALS (SSLC) FOR CONTROLLED-RELEASE

Purpose, Reverse micellar solutions of diclofenac sodium were encapsul ated in soft gelatine capsules. On contact with aqueous media they exh ibited an application induced transformation (AIT) into a semisolid sy stem of liquid crystals (SSLC) which slows down drug release. The aim of the present paper was to study in vitro and in vivo drug release fr om these systems after rectal application. Methods, In vitro, drug rel ease was determined in a self-constructed dissolution apparatus to sim ulate rectal application. For in vitro bioavailability studies rabbits were used as animal models. In vitro release and in vivo bioavailabil ity of the capsules was compared to Voltaren(R) suppositories. Results . The release profiles of the in vitro experiments show zero-order kin etics. The in vivo bioavailability studies show bioequivalence in term s of AUC for both formulations (capsules and Voltaren(R) suppositories ). The mean residence time (parameter of sustained release) of the cap sules is three time longer in comparison to Voltaren(R) suppositories. Conclusions. Rectal administration of capsules provides an appropiate route for controlled release via AIT-SSLC which could be clearly veri fied in rabbits.