20.500.12556/RUL-124781 Ugotavljanje združljivosti kalcipotriola in salicilne kisline v dermatikih Evaluation of calcipotriol and salicylic acid compatibilty in dermal preparations Luskavica je kronična kožna bolezen, ki prizadene približno 2 % svetovne populacije. Značilen bolezenski pojav je prekomerno luščenje povrhnjice. Za njeno zdravljenje uporabljamo dermatike in fototerapijo, v hujših primerih pa sistemsko terapijo. Ena od zdravilnih učinkovin za dermalno uporabo je sintetični derivat vitamina D3 kalcipotriol, ki zavira aktivnost limfocitov T in kožnih celic ter s tem zmanjšuje luščenje kože. Podatkov o njegovi stabilnosti je malo, zaradi nezdružljivosti pa ga ne moremo kombinirati s salicilno kislino. Ker ima salicilna kislina keratolitične lastnosti bi z njo dosegli sinergistični učinek kombinacije (luskavico bi zdravili po dveh poteh), dodatno pa bi olajšala prehod kalcipotriola v globje plasti kože. Zaradi pomanjkanja literaturnih podatkov smo sistematično preučili stabilnost kalcipotriola in ovrednotili njegovo združljivost s salicilno kislino. Osnova za vrednotenje je bila ustrezna stabilnostno-indikativna metoda tekočinske kromatografije visoke ločljivosti (HPLC-UV), ki smo jo najprej ustrezno ovrednotili in potrdili njeno primernost za namenjeno uporabo. Bazične raziskave stabilnosti kalcipotriola smo izvedli v raztopinah. Ugotovili smo, da je zelo nestabilen v vodnih raztopinah, njegova koncentracija pa dodatno upade pri višjih temperaturah, v prisotnosti kovinskih ionov, oksidantov, v kislih in bazičnih pogojih ter ob dodatku salicilne kisline. Stabilnost kalcipotriola smo izboljšali z uporabo metanola kot topila, v katerem je tudi v kombinaciji s salicilno kislino stabilnejši kot v vodnih raztopinah. V nadaljevanju smo ugotavljali v kolikšni meri salicilna kislina destabilizira kalcipotriol v različnih formulacijah, ki jih najdemo na slovenskem tržišču. Pred pripravo kombinacij komercialnih izdelkov s kalcipotriolom in salicilne kisline smo razvili postopek za ekstrakcijo kalcipotriola iz mazila in dermalne raztopine Sorel. Destabilizacijski učinek salicilne kisline smo preverili pri različnih temperaturah in koncentracijah in ugotovili, da se ob terapevtski koncentraciji salicilne kisline, kalcipotriol v obeh farmacevtskih oblikah skoraj v celoti pretvori že po enem dnevu shranjevanja pri sobni temperaturi. Njegovo stabilnost smo povečali z zmanjšanjem koncentracije salicilne kisline, s čimer pa zmanjšamo tudi njen učinek. Prav tako smo pri obeh oblikah zdravila Sorel ugotovili temperaturno odvisnost stabilnosti, ki se je zmanjšala pri povišani temperaturi. Psoriasis is a chronic skin condition, which affects approximately 2 % of the world population. A typical clinical occurrence is excessive peeling of the epidermis. For treatment we use dermatics and phototherapy and in severe cases systemic therapy. One of the active ingredients for dermal use is a synthetic analog of vitamin D3 calcipotriol, which inhibits the excessive activity of T lymphocytes and skin cells, therefore reducing skin peeling. There is little available data on its stability and because of incompatibility, we cannot combine it with salicylic acid. Due to the keratolytic properties of salicylic acid we would achieve a synergistic effect of the combination (treatment of psoriasis by two pathways), as well as increased calcipotriol penetration into deeper layers of the skin. Since literature data on calcipotriol stability is quite limited, we systematically studied its stability and evaluated its compatibility with salicylic acid. Evaluation was based on a stability-indicating high-performance liquid chromatography (HPLC-UV) method, which was beforehand evaluated, thus confirming its suitability for the intended use. A preliminary stability study of calcipotriol was performed on solutions. We concluded that calcipotriol is very unstable in aquatic solutions, furthermore, its concentration additionally declined at elevated temperatures, in the presence of metal ions, oxidants, in acidic and alkaline conditions, and with the addition of salicylic acid. The stability of calcipotriol was improved by using methanol as solvent, where even in combination with salicylic acid, it remained stable in comparison with aquatic solutions. Subsequently, the destabilizing effect of salicylic acid on calcipotriol was evaluated in formulations, found in Slovenia. Before preparing the combinations of commercial preparations with calcipotriol and salicylic acid, a calcipotriol extraction procedure from ointment and dermal solution Sorel was developed. The destabilizing effect of salicylic acid was evaluated at different temperatures and concentrations. We found that the therapeutic concentration of salicylic acid caused total calcipotriol degradation in both formulations after only one day of storage at room temperature. The stability was improved with lowering the concentration of salicylic acid, which consequently lowers its efficiency. Additionally, we established temperature depended stability in both forms of Sorel medication, which lowered at higher temperatures. Luskavica dermatiki kalcipotriol salicilna kislina stabilnost združljivost metoda HPLC Psoriasis dermatics calcipotriol salicylic acid stability compatibility method HPLC true false false Slovenski jezik Angleški jezik Diplomsko delo/naloga 2021-02-17 08:45:03 2021-02-17 08:45:14 2022-09-04 04:01:26 0000-00-00 00:00:00 2021 0 0 0000-00-00 NiDoloceno NiDoloceno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 1970-01-01 79873 1635.pdf 1635.pdf 1 DC2859458643E92CD26A9AF30074473E 30ff8c5870dbcfcdb7dd51d159fb897f30a879b0e5523f50103550642b048178 9f2b31c2-a1bb-11eb-a523-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=140387 Fakulteta za farmacijo 0 0 0