In recent years, numbers of researches in the field of new active pharmaceutical ingredients (API) are focused on creating new formulations with improvement on low water solubility. One of the approaches for enhancing low water solubility and low bioavailability is the formation of nanosuspensions. The nanosuspensions can be defined as colloidal dispersions of nano-sized drug particles in water. There are two main approaches to obtain them. Wet milling is a »top down« technique for reducing drug particles to the sub-micron size. During the milling process forces also have an impact on the chemical and physical stability of drugs. We made nanosuspensions with the wet ball milling in a planetary ball mill. Atorvastatine calcium (AT) was used as an active pharmaceutical ingredient, which is a selective, competitive inhibitor of HMG-CoA reductase (statin) and it is used in a treatment of the hyperlipidemia. In the first part of our research atorvastatine was milled with different polymers (hydroxypropyle methylecellulose, copovidone, poloxamer 188 and polysorbate 80). During the milling process, because of the friction between the balls, temperature increased in the milling chamber, which led to chemical instability of the atorvastatin. We analyzed this with the reverse phase chromatography. Since nanosuspensions with copovidone and poloxamer 188 had better properties (size, quantity of impurities and the possibility to produce pharmaceutical formulation) they were used in further tests. In the samples with added antioxidants (butylhydroxytoluene, rosmarinic acid) and samples prepared in the inert conditions were the least impurities we observed. During the stability testing of solid and liquid samples of nanosuspensions with copovidone and poloxamer 188 with the addition of antioxidants, we established that medium (water) is the main cause of the atorvastatin’s chemical instability. Solid samples were more stable. Our research represents a promising direction in the development of solid pharmaceutical formulations of drugs with low water solubility. Despite that, we have to be aware that with selected approach and excipients, we can not improve solubility of all poorly soluble drugs.
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