## 3 Active Ingredients of Turmeric
### Curcuminoids
#### 3.1.2 Potential Problems Related to Curcumin Application  
The available literature studies indicate an immense potential of curcuminoids in the therapy of various medical conditions, particularly the ones with underlying inflammatory pathomechanism. However, there are some difficulties related to the properties of curcumin and its derivatives that must be overcome to obtain the therapeutic effect. Curcumin and its derivatives are hydrophobic and practically insoluble in water but dissolve in organic solvents, e.g. acetone and ethanol, alkaline solvents and strongly acidic media [52]. The compounds are relatively stable in the stomach. Curcumin undergoes keto-enol tautomerism with ketone form prevailing in the acidic and neutral environment and enol form in the alkaline media. However, the highest stability was observed in media with pH exceeding 11.7, while at the physiological value of 7.4 curcumin degraded rapidly [53]. Poor solubility in water is related to another drawback of curcumin as an active ingredient, i.e. poor absorption from gastrointestinal tract and low bioavailability after oral administration, also resulting from poor permeability through biological membranes [28]. It is estimated that the bioavailability of curcumin is only about 1% after oral administration of 500 mg/kg dose [54]. Taking into consideration poor water solubility and low ability to permeate through biological barriers, curcumin is classified as Biopharmaceutics Classification System (BCS) class IV [55]. Most of the ingested drug passes through the gastrointestinal tract and is eliminated with feces, while the absorbed amount undergoes rapid metabolism in the liver. Both poor absorption and quick metabolism are considered as obstacles in terms of the therapeutic efficacy. Therefore, numerous efforts and studies have been undertaken to modify the unfavorable properties of the compound. One of the first approaches to overcome the challenges related to curcumin biopharmaceutical properties was its co-administration with piperie, an alkaloid derived from black pepper (_Pipper nigrum_) and long pepper (_Pipper longum_). It acts as an inhibitor of liver and intestinal enzymes responsible for the curcumin transformation to glucuronates. It was found that co-administration of both compounds resulted with significantly higher blood levels of curcumin when compared to curcumin administered alone [56]. It was also found that similar effects can be obtained with the use of silibinin and quercetin [57]. Other approaches are related to the systems applied as carriers for curcumin incorporation. Numerous studies describing nanoparticles [58], nano- and microemulsions [59; 60], vesicular systems [61], cyclodext [62], micelles [63], dendrimers [64] and many others indicate that the unfavorable biopharmaceutical properties of the drug can be modulated using the proper drug delivery system. As a lipophilic compound with log P value of 3.29 [54], curcumin is also a good candidate to be incorporated in self-emulsifying drug delivery systems which are known for improving poor bioavailability of the drugs displaying low solubility in water [65; 66]. In such formulations, the drug is dissolved in a mixture of oil and one or more surfactants, sometimes with additional co-surfactants and co-solvents. When the system gets to the stomach, upon the addition of gastric fluid, a fine emulsion is formed, and the drug is easily absorbed from the gastrointestinal tract. The described approach allows to improve the bioavailability of the drug and also to reduce the bioavailability differences related to interindividual variability and food effects, as it was observed for cyclosporine [67]. Another important and potentially challenging feature of curcumin is its susceptibility to chemical degradation caused by increased temperature, moisture and visible light. As a result, curcumin is transformed into ferulic acid and vanillin [68; 69]. According to [PERSON] et al.