Application of cyclodextrins in stabilization of emulsions for topical administration to the skin

Emulzije su disperzni sustavi dviju tekućina koje se međusobno ne miješaju, a sastoje se od unutarnje faze koja je u obliku kapljica raspršena u vanjskoj fazi. Danas se intenzivno proučavaju različite tehnologije izrade i fizičke stabilizacije različitih tipova emulzija. Odabir sastavnica emulzije utječe na raspodjelu veličine dispergiranih kapljica, fizičku stabilnost i reološka svojstva emulzije. Uljna faza emulzije može poslužiti kao nosač liposolubilnog lijeka ili sama po sebi imati povoljan učinak na kožu, djelujući emolijentno. Ciklodekstrini (CD) su ciklički oligosaharidi koji interakcijom s lipidima mogu fizički stabilizirati emulzije. Cilj ovo rada bio je pripremiti emulzije stabilizirane CD, prikladne za primjenu na kožu. Pripremljeni sustavi su karakterizirani s obzirom na raspodjelu veličina kapljica unutarnje faze emulzija, pH vrijednost, zeta potencijal i reološke karakteristike. U konačnici je ispitani učinak optimiranih emulzija na raspodjelu vlage na površini kože. Najprije su razvijene i karakterizirane preliminarne emulzije sastavljene od tri različite vrste ulja i stabilizirane različitim koncentracijama α-CD i HP-β-CD. U daljnja ispitivanja uključene su emulzije s tekućim parafinom, odnosno Miglyolom stabilizirane s 0,25% α-CD ili 15% HP-β-CD koje su ugušćene hipromelozom. Srednji promjer kapljica unutarnje faze smanjuje se homogenizacijom, a najzastupljenije su kapljice manje od 1 μm, zavisno o vrsti ulja i CD-a. Zeta potencijal ugušćenih emulzija varira u rasponu od -1,18 do 0,05 mV, a pH vrijednost iznosi od 5,65 do 6,40, što ih čini prikladnim za primjenu na kožu. Reološkom karakterizacijom emulzija stabiliziranih CD i ugušćenih hipromelozom, utvrđeno je da se emulzije ponašaju kao pseudoplastični sustavi te da se mogu okvalificirati kao ugušćene tekućine. S obzirom na prihvatljivu stabilnost i odgovarajuće fizikalno-kemijske karakteristike, za daljnja ispitivanja odabrane su ugušćene emulzije stabilizirane s 15% HP-β-CD i Miglyolom odnosno tekućim parafinom kao uljnom fazom. Ugušćene emulzije primjenom na kožu povećavaju sadržaj vlage u rožnatom sloju i osiguravaju hidrataciju kože kroz duži vremenski period.Emulsions are dispersed systems of two immiscible liquids consisting of an inner phase dispersed in the form of droplets in the outer one. Today, different technologies of manufacturing and physical stabilization of emulsions are intensively studied. The choice of emulsion components affects the size distribution of the dispersed droplets, the physical stability and the rheological properties of the emulsion. The oil phase of the emulsion can serve as a carrier of liposoluble drug or alone might have a beneficial effect on the skin, acting emollient. Cyclodextrins (CDs) are cyclic oligosaccharides able to physically stabilize emulsions thru interaction with lipids. This study aimed to prepare topical emulsions stabilised by CDs. The characterisation of prepared systems containing different types of lipids and CDs was performed by measuring the droplet size of the emulsion inner phase, pH value and zeta potential followed by rheological characteristics of emulsions. The effect of optimal formulations on the skin surface moisture distribution was assessed. Preliminary emulsions composed of three different types of oil and stabilized with α-CD and HP-β-CD at different concentrations were first developed and characterized. Then the emulsions containing paraffin oil or Miglyol stabilized with 0,25% α-CD or 15% HP-β-CD and thickened with hypromellose were developed. The mean droplet diameter is reduced by homogenization, and the largest proportion of emulsion droplets was below 1 μm in size, ranging from 29,4% to 36,2%, depending on the type of oil and CD. The zeta potential of the thickened emulsions was between -1,18 to 0,05 mV, with pH values in the range of 5,65 to 6,40, making them suitable for the skin application. Rheological characterization showed that the developed emulsions behave like pseudoplastic systems and can be qualified as thickened liquids. Considering the acceptable stability and the corresponding physicochemical characteristics, thickened emulsions stabilized with 15% HP-β-CD and Miglyol and liquid paraffin as the oil phase were selected for further tests. When applied to the skin, such emulsions increase the moisture content of the stratum corneum and ensure hydration of the skin over a longer time