| Abstract: |
Certain vasodilators possess a short duration of action and a decreased bioavailability due to degradation in the liver by liver enzymes (first pass effect) to different extents . Accordingly the purpose of this investigation was an approach to solve these problems.In the present investigation diltiazem Hcl, verapamil Hcl and nicardipine Hcl were formulated in different traditional transdermal formulations that are used topically on the skin for systemic action. These formulations were ointment , o/w emulsion , gel, emulgel and cellulose acetate butyrate film.The physicochemical and physicomechanical characteristics of the prepared formulations were studied.Enhancer namely, dimethyl sulfoxide (DMSO) , Tween 80 , urea ,oleic acid, lauric acid , propylene glycol, cetrimide and sodium lauryl sulphate (SLS) were added in different concentrations to the selected pharmaceutical formulations.In vitro studies were carried out on an isolated abdominal rabbit skin using diffusion cell. The amount of each drug released from the applied preparations and permeated through the rabbit skin to an appropriate receiving media were determined spectrophotometrically at a specified periods of time for six hours.The correlation coefficient (r) , the steady-state flux (J) and permeability coefficient (kp) for each drug were calculated .The obtained results clearly demonstrated that the permeation of each drug through the skin was mainly dependent on the composition of each base and the type of the added enhancer and its concentration.The best formulations that gave a better permeation through abdominal rabbit skin as follows: For diltiazem hydrochloride: cellulose acetate butyrate film and o/w emulsion base without enhancers and those containing DMSO as enhancer in a concentration of 4% and 6% respectively, showed the best permeation through the abdominal rabbit skin. For verapamil hydrochloride: cellulose acetate butyrate film and o/w emulsion base without enhancers and those containing 4% DMSO and 6% oleic acid respectively, , showed the best permeation through the abdominal rabbit skin. For nicardipine hydrochloride: o/w emulsion base and cellulose acetate butyrate film without enhancers and those containing 6% urea and 4% DMSO respectively, showed the best permeation through the abdominal rabbit skin.Then the bioavailability of the above mentioned best formulations for each drug were carried out using white male rabbits. This was done in a comparative studies between an oral administrated dose and that applied on the skin for transdermal evaluation. Blood samples were withdrawn at a specified periods of time for 8 hours and the plasma was separated. Drugs were analyzed by HPLC methods. The C max , the T max , the AUC0-8hrs and the percentage comparative bioavailability were determined. It was of great interest to demonstrate that a considerable amount of the tested drugs was absorbed through the skin and gave a reasonable concentration in the blood that maintained for a prolonged period of time. Hence ,it can be concluded that the transdermal route can be used as an alternative route to the oral drug therapy to avoid the first pass effect and to get a prolonged action.
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