Development of method for in vitro release testing of dexamethasone from oil formulation with addition of Capryol R 90

Deksametazon je često korišten lijek u kroničnoj terapiji velikog broja indikacija. Nalazi se u oralnim, oftalmičkim i parenteralnim pripravcima, no u posljednje se vrijeme puno radi na istraživanju parenteralnih formulacija koje bi imale produženo djelovanje. Takvo djelovanje bi osiguralo manje nuspojava, bolju suradljivost pacijenata i rjeđe doziranje. Uljne otopine, koje se sastoje od lijeka otopljenog u biljnom ulju s prigodnim dodacima poput suotapala, mogu poslužiti kao sustavi koji bi omogućili produljeno djelovanje lijeka. U ovom radu je ispitano nekoliko najkorištenijih ulja s dodatkom suotapala Capryola® 90 kako bi se odabralo najpogodnije ulje kao otapalo. Formulacija s ricinusovim uljem i 20% (v/v) Capryola® 90 odabrana je za razvoj in vitro metode za ispitivanje oslobađanja. Trenutno nema definirane metode za ispitivanje oslobađanja parenteralnih pripravaka produljenog oslobađanja, stoga je za ispitivanje oslobađanja odabran uređaj eng. optic fiber. Sastoji se od jedinice za oslobađanje, koju čini aparatura USP II, spregnute optičkim vlaknima za automatsko određivanje apsorbancije. Cilj rada je razviti i evaluirati in vitro metodu za ispitivanje oslobađanja deksametazona iz izabrane formulacije. Kao nosači formulacije korištene su membrane celuloza estera i regenerirane celuloze. Formulacija usporeno oslobađa deksametazon i moguće ju je upotrijebiti kao parenteralni pripravak produljenog djelovanja. Ispitivanjem utjecaja eksperimentalnih uvjeta na brzinu oslobađanja deksametazona utvrđeno je da razvijena metoda pokazuje osjeljivost na promjenu temperature, dok su profili oslobađanja slični (utvrđeno računanjem f2 Bootstrap metodom) promjenom ostalih uvjeta.Dexamethasone is frequently used drug in chronic therapy in large amount of indications. It can be found in oral, ophthalmic and parenteral products, but, lately, there has been an increasing focus on researching the parenteral formulations with prolonged release. Achieving prolonged release would reduce side effects, improve patient adherence and accomplish less frequent drug use. Lipophilic solutions, that consist of drug dissolved in vegetable oil with apposite additives such as cosolvents, can be used as systems that would enable prolonged drug release. In this study several most used vegetable oils were studied with addition of cosolvent Capryol® 90 in order to pick the most appropriate vegetable oil as solvent. The formulation that consists of ricinus oil and 20% (v/v) of Capryol® 90 was chosen for in vitro drug release testing. Currently, there are no specified methods for drug release tests for prolonged release parenterals, therefore optic fiber device was chosen for drug release testing. It consists of drug release unit which is USP II apparatus coupled with optic fibers for automatic absorbency determination. The aim of this study is to develop and evaluate in vitro method for drug release testing of dexamethasone from chosen formulation. Cellulose ester and regenerated cellulose membranes were used as formulation carriers. Dexamethasone is slowly released and formulation can be used as prolonged release parenteral formulation. By studying the effect of experimental conditions on drug release rate of dexamethasone it is concluded that the developed method is sensitive to temperature changes, while changing other conditions showed that dissolution profiles were similar (concluded by determination of f2 with Bootstrap method)