The development of oral pharmaceutical forms has often been limited by the poor solubility of active pharmaceutical ingredients. One possible solution is incorporating them into self-microemulsifying systems. Their behaviour and behaviour of active pharmaceutical ingredient following an oral application depends on the conditions in the digestive tract; one of the important parameters are physiological surface-active agents. Knowledge of the effect of various physiological parameters is important for optimizing in vitro methods for evaluating self-microemulsifying systems. The purpose of the master's thesis was to first conduct a theoretical review of published studies and to search for the physiological concentrations of bile salts and phospholipids, osmolality, and the surface tension of digestive fluids in the small intestine, and, moreover, to experimentally evaluate the release of active pharmaceutical ingredient from self-microemulsifying system in various mediums.
A systematic review of literature in the Pubmed database yielded 32 articles. Concentrations of bile salts range between 2 and 6 mM fasted state and between 7 and 15 mM after a meal.
The release of three different active pharmaceutical ingredient (dipyridamole, paracetamol, and diclofenac sodium), which were incorporated into a model self-microemulsifying system, was tested. The release was tested in HCl solution, a phosphate buffer, a tris-maleate buffer, and a digestive medium. This was done to observe the effect of different media on the release of active pharmaceutical ingredient with different physical and chemical properties from self-microemulsifying system. In total samples these do not affect the proportions of released active pharmaceutical ingredient, but in case of water samples, their influence is clearly visible. Based on the proportions of released active pharmaceutical ingredient, we found that results are consequence of solubilization with self-microemulsifying system and pH of medium, which affect the behavior of active pharmaceutical ingredient and surface-active agent. This is well illustrated by the total samples, as in the case of poor solubility of active pharmaceutical ingredient in the medium, the percentage of released active pharmaceutical ingredient is also lower. The proportions of released active pharmaceutical ingredient are slightly lower in case of water samples, which could not only be due to solubilization with self-microemulsifying system and pH, but also to the addition of 4-bromobenzeneboronic acid.
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