Study of influence of surface-active substances concentration on clopidogrel releasing from the rectal suppository

Abstract

During the last years clopidogrel which together with strong polyvalent antiaggregatory action on platelets decreases the level of triglycerides and optimizes other indexes of lipidogramm has ranked the leading place from the medications with antiplatelet mechanism. In the Ukrainian pharmaceutical market clopidogrel is presented in form of domestic and imported film-coated tablets. Alternative to oral administration of clopidogrel is rectal route which thanks to increasing of medical substance bioavailability allows to decrease the active ingredient dose and minimize the risks of unwanted side effects in the organism. At the Medicinal Preparations Technology Department of Zaporozhye State Medical University the research of composition development and technology of clopidogrel rectal dosage form for prevention of atherothromboses for the patients with myocardial infarction, acute coronary syndrome, ischemic stroke, occlusive arterial disease. As a result of biopharmaceutical investigations it was established that combination of excipients – the base (mixture of polyethyleoxydes with molecular weight 1500 and 400 in ratio 9:1) and surface-active substance (twin-80) provides optimal releasing of clopidogrel from the rectal suppository. The aim of this work is scientific substantiation of surface-active substance (twin-80) concentration in rectal dosage form with clopidogrel. Materials and methods . Suppositories were made by the fusiom method using the forms from the Franco-Krespy semi-automatic device. Concentration of surfactant (twin-80) was 0,5%, 1%, 2%, 3% and 5% of drug mass, clopidogrel content was 0,075 g in each suppository. As a parameter of optimization a clopidogrel releasing from suppository compositions was chosen as a first stage of bioavailability study. Clopidogrel releasing from the suppository was studied using the equilibrium dialysis method by Kruvchinsky at 37±0,5 0 С temperature throuth the semipermeable membrane – cellophane film «Kuprofan» in a station with Franz diffusion cells (producer is «Permegear, Inc»., USA). As a dialysis medium taking into account clopidogrel solubility methyl alcohol was chosen. Concentration of clopidogrel released after 30 min was determined by the spectrophotometric method using the spectrofotometer UV – 2600 (producer is«Shimadzu Corp»., Japan). Results . Analysis of variance showed significant influence of surfactant (twin-80) concentration on the clopidogrel releasing from the suppository compositions. Verification of average results of clopidogrel releasing by the Dunkan’s multiple rank test showed that increasing of twin-80 concentration in rectal suppository with clopidogrel more than 2% doesn’t lead to increasing of its releasing from the dosage form. Conclusions . As a result of carried out biopharmaceutical study of clopidogrel suppository it was determined that surfactant (twin-80) concentration has a statistically significant influence on its releasing from the dosage form. It was found out that 2% concentration of twin-80 provides with the optimal level of clopidogrel releasing from the rectal suppository.