Pharmaceutical development with commercialization of generic drugs with poor soluble substance – tablets of drug nimodipine

摘要

The pharmaceutical development of solid dosage forms which containing a poor soluble substance deserves special attention, because a composition and a technology of production such drugs directly effects on release the active pharmaceutical ingredient in the human body and, as a consequence, on pharmacological effectiveness of this drug. The search of therapeutically effective, economically viable and industrially reproducible technology for the production of such drugs is very important for the pharmaceutical industry.The purpose of our work was the pharmaceutical development of the generic drug, which contains a poor soluble in water substance nimodipine. The subject of the research is the substance nimodipine and the samples of tablets obtained with the help of various technological methods from this substance. All analytical and pharmaco-technological researches were implemented according to generally accepted methods that accordance with the requirements of the State Pharmacopoeia of Ukraine.Laboratory batches were developed using technological methods of physical modification of a substance, such as: micronization, sonocrystalllization, solid dispersion by melting, solid dispersion by solvent evaporation, complexation with β-cyclodextrins. Researches of the comparative in vitro dissolution kinetics of substance nimodipin from these laboratory batches made it possible to establish optimal technology for the commercial production of a generic drug. Researches on influence quantity of disintegrant and lubricant in the composition of tablets on the pharmacopoeial parameters of the quality were done.According to the results of the pharmaceutical development, it can be argued that the use of the technological method for production a solid dispersion with the aid of a solvent is most appropriate for the production of tablets of a generic drug with a substance nimodipine, which is confirmed by the results of the comparative in vitro dissolution kinetics in three media and clinical trials. The required quantity of disintegrat (not less than 2.5% per tablet) and lubricant (not less than 0.4% per tablet) in the composition of generic tablets were defined.