Browsing by Subject "kiteinen lääkeaine"

Today, many of the new drugs are poorly soluble in water, which can be a problem in the drug development. Solid dispersion is a formulation technique, which improves the dissolution rate of the drug. However solid dispersions, where the drug is in amorphous form, are often unstable. Because of that, solid dispersions, where the drug is in crystalline form, have been developed. Drug crystallization and factors affecting to the crystallization, such as amount of the polymer, are important to examine to be able to develop better drug products. Different kinds of mathematical models, which describe the kinetics of crystallization, has been developed to help to understand the crystallization event more comprehensively. In this study, the crystallization of the amorphous drug, in the absence of polymer and with a low polymer concentration, was investigated. The crystallization was also examined using a mathematical model designed to determine the kinetics of crystallization in order to find out does it work in this case. A model drug was felodipine and polymers used in this study were HPMCAS-LF and PVP K30. The concentration of polymers in the solid dispersions was 10% and 20%. It was found that a small amount of polymer has a very significant effect on crystallization rate of felodipine. Mathematically defined crystallization rate constant k increased by 13 times, when the amount of PVP was decreased 20 % to 10 %. The polymer concentration also had an effect on nucleation time which is the time before crystallization occurs. For example in the solid dispersion, where PVP concentration was 10 %, the nucleation time was five times slower and 20 % PVP consentration ten times slower than felodipine alone. The work also showed that HPMCAS stabilizes the amorphous state of felodipine better than PVP at 40 ° C / 75% RH conditions. This was observed in both MTDSC-measurements and the polarizing light microscopy. The difference between polymers was thought to be due to weakening of the interactions between PVP and felodipine by the influence of water in humid conditions. However, the different formulations had no significant effect on dissolution characteristics of felodipine. There is a possibility that felodipine crystallizes at the beginning of dissolution. It should be noted that mathematical method tested was not able to model crystallization kinetics properly in this study. So care should be given, when using a mathematical model in the product development.