Micellar solubilization of cannabinoids from industrial hemp

V današnjem času se pojavlja vedno večje zanimanje za naravna zdravila. Konopljo (Cannabis sativa) uporabljajo za različne namene že tisoče let – kot gospodarsko rastlino, v rekreativne in medicinske namene. Naravni kanabinoidi so namreč znani po številnih učinkih, tudi pozitivnih terapevtskih: delujejo kot analgetiki, antiemetiki, lajšajo težave in simptome pri nevroloških motnjah ter anoreksiji. V magistrski nalogi smo se ukvarjali z micelarno solubilizacijo kanabinoidov iz industrijske konoplje. Zanimal nas je vpliv različnih vrst površinsko aktivnih snovi na fizikalne lastnosti in stabilnost micelarnih raztopin. Izbrane raztopine smo fizikalno ovrednotili s fotonsko korelacijsko spektroskopijo in opazovali spremembe v njihovem izgledu skozi daljše časovno obdobje. Uporabili smo oljni in alkoholni ekstrakt s kanabinoidi ter tekom izdelave raztopin ugotovili, da je najprimernejši alkoholni (CBD = 50 mg/g, THC < 1,9 mg/g). Z eksperimentalnim delom smo ugotovili, da ima izbira organskega kotopila (glicerol, etanol) vpliv na povprečni premer micelov. Ekstrakt s kanabinoidi smo uspešno solubilizirali s Softigenom® 767 ter kombinacijo blok kopolimera (Lutrol® F 127) in neionske površinsko aktivne snovi (Tween® 80). Nastale so bistre raztopine z velikostjo micelov od 10 – 20 nm. Z uporabo žolčnih soli in ostalimi neionskimi PAS (natrijev lavrilsulfat) solubilizacija ni uspela, nastale so opalescentne raztopine. Enak rezultat smo dobili tudi z naravnimi emulgatorji (lecitin, arabski gumi, modificiran škrob) in β-ciklodekstrinom. S temi poizkusi smo prišli do ugotovitve, da je Tween® 80 ključen za solubilizacijo ekstrakta s kanabinoidi. Tako smo na koncu preizkusili še kombinacijo sintezne (Tween® 80) in naravne (arabski gumi) površinsko aktivne snovi. Po spremembi postopka in recepture je nastala bistra micelarna raztopina. Na podlagi rezultatov smo zaključili, da je za uspešno solubilizacijo kanabinoidov ključna pravilna izbira in kombinacija površinsko aktivnih snovi ter optimizacija formulacije.Nowadays, there is an increased interest in natural medicines. Cannabis (Cannabis sativa) has been used for various purposes for thousands of years – as an economic plant, for recreational and medical purposes. Natural cannabinoids are known for numerous effects, including positive therapeutic effects: they act as analgesics, antiemetics and they relieve problems and symptoms in neurological disorders and anorexia. In the master\u27s thesis we dealt with micellar solubilization of cannabinoids from industrial hemp. We were interested in the influence of various types of surfactants on the physical properties and stability of micellar solutions. The selected solutions were physically evaluated by photon correlation spectroscopy and we also observed changes in their appearance over a longer period of time. We used oil and alcoholic cannabinoid extracts and during the preparation of the solutions, we came to the conclusion that the most suitable one is alcoholic extract (CBD = 50 mg/g, THC < 1,9 mg/g). With the experimental work, we found out that the selection of the organic cosolvent (ethanol, glycerol) has an effect on the average diameter of the micelles. The cannabinoid extract was successfully solubilized with Softigen® 767, and a combination of block copolymer (Lutrol® F 127) and anionic surfactant (Tween® 80). Clear solutions with a micelle size of 10 – 20 nm were formed. Solubilization was not successful using bile salts and other anionic surfactants (sodium laurly sulfate), opalescent solutions were formed. The same result was obtained with natural emulsifiers (lecithin, arabic gum, modified starch) and β-cyclodextrin. With these experiments, we came to the conclusion that Tween® 80 is crucial for the solubilization of the cannabinoid extract. At the end we tested a combination of synthetic (Tween® 80) and natural (arabic gum) surfactant. After changing the process and the recipe, a clear micellar solution was formed. Based on results we have come to the conclusion, that the correct choice and combination of surfactants, and also optimization of the formulation is crucial for successful micellar solubilization of cannabinoids