Preparation and characterization of rebamipide nanocrystals

Tehnologija nanokristala intenzivno se razvija te se njezinom primjenom u farmaceutskoj industriji nastoje poboljšati biofarmaceutska i farmaceutsko-tehnološka svojstva djelatnih tvari. Nanokristali su čestice veličine od 1 do 1000 nm te povećavaju brzinu otapanja povećanjem specifične površine tvari. Metoda proizvodnje nanokristala ovisi o fizikalno-kemijskoj prirodi djelatne tvari, a dvije glavne skupine metoda izrade su metoda smanjenja veličina čestica (engl. top-down methods) i metoda povećanja veličine čestica (engl. bottom-up methods). Složenost strukture oka predstavlja ograničenje za isporuku lijekova te su se formulacije temeljene na nanokristalima pokazale uspješnima u postizanju povećanja vremena zadržavanja, bioraspoloživosti i propusnosti lijekova kroz očne barijere. Za liječenje problema suhog oka na tržištu je dostupna 2% suspenzija rebamipida koja nakon primjene uzrokuje kratkotrajno zamućenje vida zbog mliječno-bijelog izgleda. U ovom radu pripravljene su nanosuspenzije rebamipida uz dodatak površinski aktivnih tvari Polisorbat 80 i Pluronic F-68 u različitim udjelima. Nanosuspenzije su izrađene metodom vlažnog mljevenja te je izmjerena veličina čestica, indeks polidisperznosti i udio kristalinične frakcije lijeka. Iz dobivenih je rezultata zaključeno da su najbolji rezultati postignuti u nanosuspenzijama koje su sadržavale 0,25%, odnosno 0,5% površinski aktivne tvari. Izgled nanosuspenzije ostao je i dalje mliječno-bijeli unatoč tome što je u svim uzorcima veličina čestica bila manja od 400 nm.Nanocrystal technology is intensely being developed and with its application in the pharmaceutical industry, the biopharmaceutical and pharmaceutical-technological properties of active ingredients are trying to be improved. Nanocrystals are particles with size from 1 to 1000 nm and they increase the dissolution rate by increasing the specific surface area. The method of nanocrystal production depends on the physicochemical nature of the active ingredient, but the two main groups of methods are methods that decrease the particle size (top-down methods) and methods that increase the particle size (bottom-up methods). The complexity of the eye structure presents as the limit for the drug delivery and formulations based on nanocrystals have shown themselves successful in achieving increased retention time, bioavailability and drug permeability through barriers of the eye. For the dry eye treatment a 2% rebamipide suspension is available on the market which after its application causes short-term blurred vision because of its milky-white appearance. In this study rebamipide nanosuspensions have been made with the addition of surfactants Polisorbate 80 and Pluronic F-68 in different ratios. The nanosuspensions were made using the wet grinding method and the particle size, polydispersity index and proportion of the crystalline fraction of the drug were measured. From the collected results it was concluded that the best results were accomplished in nanosuspensions that contained 0.25% and 0.5% of surfactants. The appearance of the nanosuspension remained milky-white despite the fact that in all samples the particle size was lesser than 400 nm