E.V. Kompantseva, A.M. Shevchenko, A.V. Bab-yak

Against the background of the ongoing research in the field of treatment of hypertension in recent years, more attention was to involve combination therapy with the fixed-dose preparations. In this regard, the development of the domestic combination product containing calcium antagonist verapamil hydrochloride and angiotensin-converting enzyme inhibitor lisinopril dihydrate in the ratio 1:10 is of definite interest. Composition is a complex formulation which prolonged effect should be provided by verapamil. The aim of the research was to develop the optimal composition and conditions of verapamil sustained release tablets. MATERIALS AND METHODS. A dose of verapamil 100 mg was divided into 4 tablets (4-6 mm diameter) of 25 mg and placed in a capsule. For obtaining verapamil sustained release tablets the method of wet granulation was used. Definition of technological characteristics of granulates and model tablets was performed according to normative documents 42-0137-09 and 42-0132-09, respectively. The test for the release of a substance in a solution of verapamil was carried out on the apparatus such as «rotating basket» in accordance with the normative document 42-0135-09. The content of verapamil was determined by spectrophotometry method at 278 nm. RESULTS AND DISCUSSION. Analysis of the composition of tablets with sustained release of the drug showed that in the capacity of matrices for the release, combinations of water-soluble polymers natural or synthetic origin with microcrystalline cellulose were the frequently used. Six compositions were developed and tested to create a long-acting formulation of verapamil. The results of identifing the main technological parameters of the model composition of verapamil granules showed that the optimal matrix is a composition of sodium alginate, and microcrystalline cellulose with Plasdone K-90 (composition № 5) or Plasdone K-30 (composition № 6). The next and the main criterion of selection of optimal prescription excipients of verapamil tablets is the test for the release of substances in solution. On the hydraulic press different compacting pressure (25 to 125 MN/m2) for obtaining verapamil tablets of composition № 5 and № 6 was created. The tests were conducted on six samples for each value of the compacting pressure. The results of tests of verapamil tablets of composition № 5 showed that the optimal values of the released substance (according to regulations of normative document) is achieved by using compacting pressure of 125 MN/m2. However, in the industrial production applying of this pressure is undesirable. In testing the release of substances in the solution of verapamil model tablets of composition № 6 satisfactory results were obtained only in the first hour of dissolution at a pressure of 25 and 50 MN/m2. In this regard, we have been requested to enter into a pharmaceutical composition of 4 tablets of verapamil obtained at different compacting pressures (from 25 to 100 MN/m2). This method allowed to obtain the optimal release profile of the active substance in the solution. CONCLUSIONS. In the course of experimental work the composition of verapamil tablets was developed. It is shown that the optimal prolonged effect is achieved by using a matrix of sodium alginate, microcrystalline cellulose and Plasdone K-90. This matrix, as well as technological method of receiving the 4 tablets of verapamil with successively increasing compaction pressure, provides a uniform release of the active ingredient over time.