CONTROLLED IONTOPHORETIC DELIVERY OF NARCOTICS

THE AIM OF THIS PROPOSAL IS TO INVESTIGATE AND DEVELOP LONG-TERM IONTOPHORETIC PROCEDURES FOR DELIVERY OF NARCOTIC AGENTS. IONTOPHORESIS HAS BEEN KNOWN FOR A LONG TIME, BUT ITS APPLICATION IS LIMITED TO SHORT-TERM PROCEDURES (15 TO 30 MINUTES). THE MAJOR IMPEDIMENT TO LONG-TERM USE IS THE FORMATION OF ELECTROLYTIC PRODUCTS AT THE ELECTRODE, LOWERING THE EFFICIENCY OF DRUG TRANSPORT AND CAUSING BURNS. THESE PROBLEMS HAVE BEEN ADDRESSED AND LONG-TERM DELIVERY HAS BEEN STUDIED BOTH THEORETICALLY AND EXPERIMENTALLY WITH MORPHINE AS A MODEL DRUG. AS A RESULT, TREATMENT TIMES HAVE BEEN EXTENDED UP TO 2 HOURS WITH SIGNIFICANT MORPHINE LEVELS IN BLOOD AND NO COMPLICATIONS. THE PROPOSED STUDY INVOLVES (1) LABORATORY IN VITRO DETERMINATIONS OF IONTOPHORETIC ELECTRODE EFFICIENCY AND DELIVERY RATES OVER LONG (12 TO 24 HOURS) APPLICATION TIMES USING AN AUTOMATED, COMPUTER-CONTROLLED SAMPLING SYSTEM; (2) ANIMAL EXPERIMENTS USING NUDE RATS WITH ISOLATED SKIN FLAPS IN ORDER TO DETERMINE LONG-TERM DELIVERY RATES WITH (14)C MORPHINE HC1; AND (3) A CONTROLLED, DOUBLE-BLIND CLINICAL STUDY INVOLVING PATIENTS AFFLICTED BY SEVERE POSTOPERATIVE PAIN. THE RESULT OF THESE STUDIES WILL BE A NEW IONTOPHORETIC DRUG DELIVERY SYSTEM FOR NARCOTIC ANALGESICS, PRIMARILY MORPHINE. IN PHASE II, NEW ELECTRODE FORMULATIONS AND AN IONTOPHORETICCONTROL DEVICE WILL BE DESIGNED, FABRICATED, AND USED IN LARGE-SCALE, LONG-TERM CLINICAL TRIALS.