| Abstract | Melatonin je neurohormon koji se istražuje za liječenje raznih bolesti i stanja. Broj istraživanja dermalnih formulacija melatonina raste zbog njegovog potencijala u liječenju upalnih bolesti kože, sprječavanju znakova starenja, zaštiti kože od UV zračenja i zacjeljivanju rana. Dermalni put primjene lijeka omogućuje jednostavnost korištenja i postizanje visoke koncentracije lijeka izravno na mjestu primjene. Gelovi za dermalnu primjenu omogućuju dulje zadržavanje djelatne tvari na mjestu primjene te produljeno oslobađanje uklopljenog lijeka. Cilj ovog rada bio je odrediti biofarmaceutska svojstva karbopolskog gela s melatoninom za dermalnu primjenu. Pripravljen je gel karbopola (0,1 %, m/m) i polietilenglikola (PEG-a; 5 %, m/m) s uklopljenim melatoninom (0,1 %, m/m; formulacija CPM). Termodinamička topljivost melatonina u fiziološkoj otopini puferiranoj fosfatnim puferom (pH 7,4) iznosila je 1,34 ± 0,08 mg/ml, a u fosfatnom puferu (pH 5,5) 1,60 ± 0,22 mg/ml. Ispitivanjem in vitro oslobađanja melatonina, CPM formulacija je, u usporedbi s kontrolnom otopinom, karakterizirana produljenim oslobađanjem lijeka. Zabilježeno je nešto brže oslobađanje melatonina iz CPM-a pri pH 7,4 u usporedbi s medijem pH vrijednosti 5,5, no razlika nije pokazana statistički značajnom (f2 = 52,86). Usporedba dobivenih profila oslobađanja melatonina iz CPM-a u oba medija s poznatim matematičkim modelima pokazala je najbolju podudarnost s Korsmeyer-Peppasovim modelom. Difuzija melatonina iz formulacije pratila je Fickov mehanizam. Vijabilnost od 82,5 ± 4,3 % određena MTT testom potvrdila je biokompatibilnost formulacije CPM. Biofarmaceutska karakterizacija provedena u ovom radu ukazuje na potencijal formulacije CPM kao farmaceutskog oblika za dermalnu primjenu melatonina. |
| Abstract (english) | Melatonin is a neurohormone currently under investigation for the treatment of various diseases and conditions. The number of studies on dermal melatonin formulations is increasing, due to its potential in treating inflammatory skin diseases, preventing signs of aging, protecting the skin from UV radiation, and promoting wound healing. The dermal drug administration route enables the simplicity of application and high drug concentration at the site of application. Dermal gels enable prolonged retention of the active substance at the application site and its prolonged release. The aim of this study was to determine the biopharmaceutical properties of a carbopol gel with melatonin for dermal administration. The gel was prepared using carbopol (0.1%, w/w) and polyethylene glycol (PEG; 5%, w/w) with the addition of melatonin (0.1%, w/w; CPM formulation). The thermodynamic solubility of melatonin in phosphate buffered saline (pH 7.4) was 1.34 ± 0.8 mg/mL, and 1.60 ± 0.22 mg/mL in phosphate buffer (pH 5.5). In vitro release study showed the prolonged melatonin release from CPM formulation compared to the control solution. A slightly more rapid release of melatonin from CPM was observed at pH 7.4 compared to the medium with a pH value of 5.5, but the difference was not statistically significant (f2 = 52.86). Comparison of the melatonin release profiles from CPM in both media with known mathematical models showed the best fit with the Korsmeyer-Peppas model. The diffusion of melatonin from the formulation followed Fickian mechanism. The viability of 82.5 ± 4.3% determined by the MTT assay confirmed the biocompatibility of the CPM formulation. Biopharmaceutical characterization performed in this study indicates the potential of the CPM formulation as a pharmaceutical form for dermal application of melatonin. |
