Solubility assessment of cannabidiol in different solvents

Navadna konoplja (Cannabis sativa, L.) je rastlina, ki jo človeštvo s pridom izkorišča že tisočletja. V konoplji je prisotnih preko 100 kanabinoidov, med katerimi sta najpomembnejša kanabidiol (CBD) in tetrahidrokanabinol (delta-9-THC). Farmakološki učinek pri vretenčarjih dosežeta z delovanjem na kanabinoidne in nekatere druge receptorje. THC je psihotropna substanca in zaradi tega zakonodajno regulirana kot prepovedana droga v veliko državah. Drugače velja za CBD, ki ni psihoaktiven in zato bolj varen za uživanje. V zadnjih desetih letih se je njegova uporaba v farmaciji, hrani in kozmetiki močno povečala. Vedno bolj je tudi poznan javnosti. Na tujih trgih sta že 2 zdravili, ki vsebujeta CBD (Epidyolex in Sativex). Kljub temu je v literaturi malo podatkov, ki opisujejo njegovo topnost v različnih topilih. Zato smo v magistrski nalogi določili topnost CBD v topilih, ki so za njegovo uporabo najbolj pomembna. Najprej smo raziskali spletni trg izdelkov s CBD, pri katerih so prevladovale kapljice in pršila, da smo ugotovili, katera topila se najpogosteje uporabljajo. Zadetke smo v spletnem brskalniku iskali v slovenščini in angleščini. Največkrat so pregledani izdelki kot nosilna topila vsebovali MCT olje, olje konopljinih semen, olivno olje in njihove zmesi. Zato smo topnost določili v vseh treh omenjenih oljih. Poleg tega smo topnost določili tudi v čijevem olju, propilenglikolu (in njegovih vodnih raztopinah), trietil citratu, PEG 400, triacetinu, 96% etanolu, metanolu, izooktanu, acetonu, izopropanolu, DMSO, 1-butanolu, DMF, cikloheksanu, diklorometanu in dietiletru. Za določanje topnosti smo uporabili »shake-flask« metodo, pri čemer smo pripravili suspenzije CBD (na sobni temperaturi), jih stresali 48 h na stresalniku, filtrirali, redčili in določili koncentracijo CBD s HPLC metodo. CBD je v vodi zelo slabo topen, vendar to ne velja za večino drugih topil, v katerih smo določali topnost. Najbolje so ga raztapljali aceton, metanol in dietileter ter le malenkost slabše ostala laboratorijska topila. Tudi v topilih, ki se uporabljajo za izdelavo izdelkov, je bil CBD zelo dobro topen. Med njimi je bila topnost najvišja v triacetinu, PEG 400 in trietil citratu. Nekoliko slabša je bila v propilenglikolu in še nižja v rastlinskih oljih. V vodnih raztopinah propilenglikola se je izkazalo, da že nizka vsebnost vode močno zniža topnost CBD. Med rastlinskimi olji je bil CBD najbolje topen v MCT olju, najslabše pa v olivnem olju.Cannabis (Cannabis sativa, L.) is a plant that has been used by mankind for thousands of years. It contains over 100 cannabinoid molecules, the most important of which are cannabidiol (CBD) and tetrahydrocannabinol (delta-9-THC). They achieve their pharmacological effects on vertebrates by acting on cannabinoid receptors and some other receptors. THC is a psychotropic substance and is therefore highly regulated as an illicit drug by most authorities around the world. CBD on the other hand is not psychotropic and has a more favorable safety profile. Over the last ten years, its use has increased significantly as has its recognition among the general public. There are already two CBD-containing medicines on the market (Epidyolex and Sativex). Nevertheless, there is little data in the literature describing its solubility in various solvents. Therefore, we determined the solubility of CBD in the solvents that are most important for its use. Firstly, we researched the online market of CBD products (drops and sprays) to find out which solvents are most commonly used. We searched for results in the web browser in Slovene and English language. The reviewed products most often contained following carrier solvents: MCT oil, hemp seed oil, olive oil, and their mixtures. Therefore, we determined the solubility in all 3 mentioned oils. We also measured the solubility of CBD in chia seed oil, propylene glycol, and its aqueous mixtures, triethyl citrate, PEG 400, triacetin, 96 % ethanol, methanol, isooctane, acetone, isopropanol, DMSO, 1-butanol, dimethylformamide, cyclohexane, dichloromethane, and diethyl ether. Solubility was determined by using shake-flask method. Firstly, CBD suspensions were prepared (at room temperature), then shaken for 48 h on a shaker, filtered, and diluted. Then the CBD concentration was determined by the HPLC method. CBD is very poorly soluble in water in contrast to most other solvents we tested. Measured solubility was highest in acetone, methanol, and diethyl ether, followed by other laboratory solvents. CBD was also very soluble in the solvents that are often used for production of CBD products. Among them, solubility was highest in triacetin, PEG 400, and triethyl citrate. It was slightly worse in propylene glycol and even lower in vegetable oils. By adding water to propylene glycol, we discovered that even a small addition of water greatly reduces the solubility of CBD. Among vegetable oils, CBD was most soluble in MCT oil and least soluble in olive oil