Some aspects of developing the production technology for combined tablets based on B vitamins

SUMMARY

The studies in selecting the optimal technology for obtaining a combined dosage form – tablets based on B vitamins, namely selection of the rational tableting method and the method of introduction of the active substances and excipients into the tableting blend, as well as the optimal drying mode for the pyridoxine hydrochloride granulate, have been performed. For this purpose the properties of active pharmaceutical ingredients, which precondition the technological characteristics of individual powders affecting the functional characteristics of the drug, have been studied. The studies of the technological properties of the active substances of the combined tablets such as flowability, slope angle, tapped density, and compressibility have been conducted. The benfotiamine substance has a good flowability, which indicates the possibility of applying the method of the direct compression. The pyridoxine hydrochloride powder has a poor flowability as indicated by the results of studies of flowability, slope angle, compressibility and density. Such different structure of powders of the active ingredients indicates additional difficulties in choosing the optimal technology of introduction of the active ingredients into the formulation. Three batches of the tableting blend with different methods of introduction of the active ingredients and excipients have been tested. It has been determined that when wetting the tableting blend containing benfotiamine and pyridoxine hydrochloride the increase of the quantitative content of thiamine o-monophosphate impurity is observed. Therefore, removal of benfotiamine from the mixture at the lubrication stage or the use of the technology of obtaining two individual granulates with the active substances eliminated the issue of formation and increase of thiamine o-monophosphate impurity. The optimal mode of drying of the pyridoxine hydrochloride granulate has been chosen; it is 55-65°C for 60-70 min, and it allows to obtain the pyridoxine hydrochloride granulate with the optimal moisture content (not more than 5.0%).