Preformulation studies in development of nanoemulsions loaded with ibuprofen

Bolest suhog oka karakterizirana je hiperosmolarnošću suznog filma i subakutnom upalom. Trenutno su glavne terapijske mogućnosti nadomještanje suznog filma, stimulacija stvaranja suza i topikalni protuupalni lijekovi. Protuupalna nesteroidna djelatna tvar ibuprofen ima potencijal za liječenje blagog do umjereno teškog oblika bolesti suhog oka. U/V nanoemulzije predstavljaju farmaceutski oblik pogodan za uklapanje ibuprofena, a zbog nadoknade i stabilizacije suznog filma koje osiguravaju pomoćne tvari nanoemulzija moguć je razvoj vrlo učinkovitog lijeka. Cilj ovog diplomskog rada bio je provesti ispitivanje topljivosti ibuprofena u uljima koja su odobrena ili velikog potencijala za oftalmičku primjenu te razviti preliminarne nanoemulzije U/V tipa s uklopljenim ibuprofenom. Topljivost ibuprofena ispitana je u četiri ulja: ricinusovo ulje, sezamovo ulje, sojino ulje te Miglyol® 812, od kojih ricinusovo ulje karakterizira najveća topljivost ibuprofena. U sljedećoj fazi izrade diplomskog rada ispitana je mogućnost izrade nanoemulzija s uklopljenim ibuprofenom. Uljnu fazu su činili ibuprofen i ricinusovo ulje, a vodenu fazu neionska površinski aktivna tvar Tween® 80, sredstvo za izotonizaciju glicerol te pročišćena voda. Nanoemulzije su pripravljene visokoenergetskom metodom mikrofluidizacije, nakon čega su im određena fizičko-kemijska svojstva uključujući veličinu kapljica i raspodjelu veličina te zeta-potencijal. Pripravljene preliminarne nanoemulzije karakterizira odgovarajuća uklopljenost ibuprofena, veličina kapljica i raspodjela veličina te zeta-potencijal, stoga predstavljaju dobar temelj za daljnji razvoj oftalmičke nanoemulzije s uklopljenim ibuprofenom za liječenje bolesti suhog oka.Dry eye disease is characterized by hyperosmolarity of the tear film and subacute inflammation. Currently, the main therapeutic options are tear replacement, stimulation of tear production and topical anti-inflammatory drugs. The anti-inflammatory non-steroidal active ingredient ibuprofen has the potential to treat mild to moderate dry eye disease. U/V nanoemulsions represent a dosage form suitable for loading ibuprofen and due to compensation and stabilization of the tear film provided by excipients of the nanoemulsions, development of a very effective drug is possible. The aim of this thesis was to test the solubility of ibuprofen in oils that are approved or have high potential for ophthalmic use and to develop preliminary o/w nanoemulsions loaded with ibuprofen. The solubility of ibuprofen was tested in four oils: castor oil, sesame oil, soybean oil and Miglyol® 812. Castor oil is characterized by the highest solubility of ibuprofen. In the next phase of this thesis, the possibility of preparing nanoemulsions loaded with ibuprofen was examined. The oil phase consisted of ibuprofen and castor oil, and the water phase consisted of the nonionic surfactant Tween® 80, an isotonizing agent glycerol and purified water. Nanoemulsions were prepared using a high energy microfluidization method, after which their physicochemical properties were determined, including droplet size, size distribution and zeta potential. The prepared preliminary nanoemulsions are characterized by appropriate incorporation of ibuprofen, droplet size, size distribution and zeta-potential, therefore they represent a good basis for further development of an ophthalmic nanoemulsion loaded with ibuprofen for the treatment of dry eye disease