Accelerated stability testing of cationic nanoemulsions

Apsorpcija i posljedično bioraspoloživost topikalnih oftalmičkih lijekova je ograničena zbog barijera prednjeg dijela oka kao što su nazolakrimalna drenaža, refleks treptanja i suzenja, čvrste barijere rožnice te proteini i metabolički enzimi suzne tekućine. S ciljem povećanja bioraspoloživosti oftalmičkih lijekova, smanjenja nuspojava zbog neproduktivne apsorpcije u sistemsku cirkulaciju te smanjene učestalosti doziranja istražuju se i razvijaju inovativni farmaceutski oblici topikalnih oftalmičkih lijekova. Potencijal U/V nanoemulzija u oftalmičkoj primjeni temelji se na sličnosti nanoemulzija sa suznim filmom. Kako je većina oftalmičkih lijekova slabo topljiva u vodi, uklapanjem u uljnu fazu U/V nanoemulzija povećava se njihova topljivost. S ciljem produljenja zadržavanja nanoemulzija na površini oka, površina kapljica modificira se dodatkom kationskih surfaktanata ili polimera. Time površina kapljica unutarnje faze postaje pozitivno nabijena. Ključan parametar u procesu razvoja konačnog oblika lijeka je njegova stabilnost. Cilj ovog diplomskog rada je ispitati stabilnost kationskih U/V nanoemulzija čiju uljnu fazu čini Mygliol 812, surfaktanti koji osiguravaju stabilnost sustava su lecitin S45 i Cremophor EL, a pseudoemulgator kationski polimer kitozan. Nanoemulzije su pripravljene visokoenergetskom metodom mikrofluidizacije. Ispitativana je stabilnost nanoemulzija nakon skladištenja 30 dana pri sobnoj temperaturi i pri 4C, metodama ubrzanog starenja i nakon razrjeđenja umjetnom suznom tekućinom. Kao parametri stabilnosti, razmatrani su veličina kapljica, indeks polidisperznosti i zeta potencijal nanoemulzija. Određivanje stabilnosti nanoemulzija u stvarnom vremenu pri 4 i 25C ukazuju na potrebu čuvanja nanoemulzija pri nižim temepraturama. Nakon provedenih testova ubrzanog starenja, došlo do porasta veličine kapljica i indeksa polidisperznosti kationskih nanoemulija, koje prati i blagi porast zeta potencijala, ali nije došlo do vrhnjenja niti do odvajanja faza, što ukazuje na dobru kinetičku stabilnost formulacija. Miješanjem nanoemulzija sa suznom tekućinom u omjeru 40:7 nije došlo do značajne promjene veličine kapljica, indeksa polidisperznosti ni zeta potencijala kationske nanoemulzije.The absorption and consequently the bioavailability of topical ophthalmic drugs is limited by the anterior eye segment barriers such as nasolacrimal drainage, reflex blinking, tight corneal barriers and proteins and metabolic enzymes of tear fluid. In order to increase the bioavailability of ophthalmic drugs, reduce the side effects due to unproductive absorption into systemic circulation and reduced dosage frequency, innovative pharmaceutical forms of topical ophthalmic drugs are being investigated and developed. The potential of O/W nanoemulsion in ophthalmic drug delivery is based on the similarities of the nanoemulsion with the tear film. Since most of the ophthalmic drugs are poorly soluble in water, their encapsulation into the O/W nanoemulsion oil phase increases drug solubility. With the aim of prolonging the nanoemulsion retention on the surface of the eye, the droplet surface is modified by addition of cationic surfactants or polymers, which makes the droplets positively charged. The key parameter in the process of developing a final dosage form is its stability. The aim of this thesis is to examine the stability of the cationic O/W nanoemulsion whose oil phase makes the Mygliol 812, surfactants lecithin S45 and Cremophor EL, and pseudo-emulsifier cationic polymer chitosan. Nanoemulsions were prepared by a high-energy microfluidization method. The stability of nanoemulsion was tested after storage for 30 days at room temperature and at 4 ° C, accelerated stability testing methods and after dilution with simulated tear fluid. As stability parameters, the size of the droplet, the polydispersity index and the zeta potential of the nanoemulsion were considered. Determination of the stability of the nanoemulsion in real time at 4 and 25C indicates the need to store the nanoemulsion at lower temperatures. After accelerated aging tests were performed, the droplet size and polydispersity index of cationic nanoemulsion increased, followed by a mild increase in potency, but there was no creaming or phase separation, indicating good kinetic stability of the formulationsMixing the nanoemulsion with the simulated tear fluid at a ratio of 40: 7 did not induced any significant changes to the droplet size, polydispersity index nor zeta potential