ASCOLONG, A NEW BUCCAL DOSAGE FORM OF ASPIRIN

Ye.V. Kokurina, Z.A. Suslina, G.L. Khromov, A.B. Davydov, V.I. Metelina, V.G. Ionova, M.M. Tanashyan, Ye.G. Demina, Ye.V. Bochkareva, V.G. Belolilipetskaya, A.D. Deyev, N.G. Kucheryavaya, S.I. Zidra, N.N. Gorin, D.O. Rumyantsev
Research Institute of Neurology, Russian Academy of Medical Sciences,
State Research Centre of Preventive Medicine, All-Russian Research and Experimental Institute of Medical Technology, Central Research Institute of Stomatology, Ministry of Public Health of the Russian Federation,
Moscow, Russia

The aim of the present work was to study tolerance, the pharmacodynamic and pharmacokinetic properties of ascolong, a new buccal dosage form of aspirin containing a very low dose (12.5 mg) of acetylsali-cylic acid (ASA). The study included 43 normal subjects (drugtolerance evaluation) and 19 subjects, suffering from coronary artery disease (CAD) or cerebrovascular diseases. In 10 patients, the antiaggregation effect of ascolong administered in a single dose or regularly (for 2 weeks) in a dose of 12.5 mg was studied comparatively to placebo, 9 patients underwent a randomised crossover study of ascolong and aspirin tablets produced in Russia. The patients were administered the drugs in a dose of 100 mg given in courses for 2 weeks. Platelet aggregation was evaluated on the first and 14-th day of each course initially, 2, 4 and 24 hours after drug intake. It has been demonstrated that ascolong given in a single dose or regularly exerts a significant antiaggregation effect, although it is less pronounced as compared to that produced by aspirin tablets. Of the 19 patients, 13 were evaluated for the profile of blood ASA concentration after 30 minutes and hourly for 4 hours following ascolong administration. The concentration of ASA taken in a single dose varied from 27.7 to 96.8 ng/ml whereas at regular treatment it ranged within 25.2 to 70.5 ng/ml. The concentration of salicylic acid (SA), the main ASA metabolite, having a comparatively low antiaggregation activity was substantially lower than ASA concentration. Of the 9 patients who underwent cross-over treatment with ascolong and aspirin tablets, 4 were compared for the profiles of both drug concentration for 5 hours. One hour following successive intake of 100 mg of aspirin tablets blood ASA concentration constituted about 180 ng/ml whereupon the blood showed only traces of ASA concentration. At the same time the regular intake of ascolong in a daily dose of 12.5 mg provided a relatively stable drug concentration, at the level approximating 60-90 ng/ml for 5 hours whereas after 6 hours the minimal therapeutic concentration of ASA. (10 ng/ml) in blood was preserved. Transbuccal delivery of ASA to the systemic circulation leads to deceleration of its metabolism owing to which the microdose of ASA exerts a demonstrable antiaggregation effect. The drug is well tolerated. So, the buccal film dosage form of aspirin designed for the first time contains a very low dose of ASA which exerts a significant antiaggregation effect and differs from aspirin tablets in the pharmacokinetic properties.

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