Razvoj in vitro metode za ispitivanje oslobađanja deksametazona iz uljnih formulacija s dodatkom izopropanola i Capryola 90

master's thesis

• Title (english): Development of in vitro method for dexamethasone release testing from an oily solution with addition of isopropanol and Capryol 90
• Author: Viktor Novak
• Mentor: Biserka Cetina Čižmek (mentor)
• Committee member: Biserka Cetina Čižmek (predsjednik povjerenstva)
• Committee member: Anita Hafner (član povjerenstva)
• Committee member: Jelena Filipović-Grčić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; Zagreb
• Defense date and country: 2021-02-26, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Terapijsko djelovanje mnogih lijekova može se poboljšati formuliranjem u obliku pripravaka produljenog oslobađanja. Produljeno
djelovanje lijeka ima poseban značaj kod tretmana kroničnih bolesti jer se na taj način smanjuje učestalost primjene lijeka što je
prihvatljivije i za pacijenta i za zdravstveni sustav. Deksametazon je glukokortikoid koji se koristi za liječenje niza kroničnih
oboljenja. Prethodni radovi pokazali su da deksametazon u obliku uljne otopine s dodatkom suotapala ima moguću korisnu
primjenu zbog svojstva produljenog oslobađanja. U tim radovima ispitivani su mnogi parametri oslobađanja, ali je uočena potreba za dodatnim provjeravanjem metode u duljem vremenu trajanja ispitivanja zbog moguće pojave interferencija. Cilj ovog rada bio je optimizirati metodu oslobađanja deksametazona iz uljnih otopina na USP II uređaju spregnutom optičkim probama te ispitati potencijalne interferencije. Kao otapalo je korišteno ricinusovo ulje jer je u njemu deksametazon pokazao najbolju topljivost u odnosu na ostala ispitana ulja. Izopropanol i Capryol®90 kao suotapala omogućuju povećanu topljivost deksametazona u ulju, a osim toga smanjuju viskoznost otopine što dovodi do povećanja injektibilnosti. Ispitivanje je provedeno pomoću USPII uređaja spregnutog optičkim probama koje su preko apsorbancije u receptorskom mediju pratile koncentraciju oslobođenog deksametazona iz formulacija. Određen je i apsorpcijski profil placebo formulacija, a u drugom dijelu rada uvedeno je i kontrolno određivanje količine oslobođenog deksametazona UPLC-om kako bi se mogle preciznije odrediti interferencije prililkom očitavanja optičkim probama. Rezultati istraživanja pokazuju kako zaista dolazi do pojave interferencije, odnosno do prevelikog očitavanja količine oslobođenog deksametazona kod formulacije s izopropanolom nakon 36. sata i kod formulacije s Capryolom®90 nakon 24. sata od početka provođenja pokusa. Interferencija nastaje najvjerojatnije zbog otpuštanja pomoćnih sastojaka iz formulacija. Iz toga se zaključuje kako je metoda direktnog određivanja oslobađanja deksametazona pomoću optičkih proba pouzdana za analizu do 24 sata. Nadalje, budući da se nakon 24 sata oslobodi već oko 80% deksametazona iz obje formulacije, može se zaključiti kako je metoda ipak dovoljno dobra za usporedbu brzine oslobađanja između različitih uljnih formulacija deksametazona i njihov početni probir.

Abstract (english)

The therapeutic effect of many drugs can be improved in the form of prolonged release preparations. Prolonged action of the drug is of particular importance in the treatment of chronic diseases because it reduces the frequency of drug use which is more acceptable for both the patient and the healthcare system. Dexamethasone is a glucocorticoid used to treat a number of chronic diseases. Previous works have shown that dexamethasone in the form of an oil solution with the addition of a cosolvent has a possible useful application due to its prolonged release properties. In these works, many release parameters were examined, but there was still a need for additional verification of the method over a longer duration of the test due to the possible occurrence of interferences. Therefore, the aim of this work was to optimize the method for dexamethasone release from oil solutions on a USP II device coupled with optic fiber spectrophotometer and to examine potential interferences. Castor oil was used as a solvent due to highest dexamethasone solubility compared to other tested oils. Isopropanol and Capryol®90 as cosolvents increase solubility of dexamethasone in oil, and in addition reduce the viscosity of the solution leading to increased injectability. The assay was performed on a USPII device coupled with optical fibers that monitored the concentration of dexamethasone released from the formulations via absorption in receptor medium. The absorption profile of placebo formulations was determined and in the second part of the assay additional measurement of released dexamethasone by UPLC was introduced so that interferences during optical probes detection could be determined more precisely. The results of the study confirmed the existence of interference by optical probes detection, meaning that there is an excessive detection of released dexamethasone in the formulation with isopropanol after
36 hours and with Capryol®90 after 24 hours duration of the experiment. Interference occurs most likely due to the release of excipients from the formulations. Therefore, method of direct determination of dexamethasone release by optical fibers is reliable for analysis up to 24 hours. Furthermore, since about 80% of dexamethasone is released from both formulations after 24 hours, the method is still good enough to compare the release rate between different dexamethasone oil formulations as well as for for their initial screening.

• Keywords: deksametazon; ricinusovo ulje; izopropanol; Capryol®90; uljna otopina; USPII; ispitivanje oslobađanja; spektrofotometrija; optička proba
• Keywords (english): dexamethasone; castor oil; isopropanol; Capryol®90; oily solution; USPII; dissolution testing; spectrofotometry; optic fiber
• Language: croatian
• URN:NBN: urn:nbn:hr:163:715437
• Study programme: Title: Pharmacy; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: magistar/magistra farmacije (magistar/magistra farmacije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2022-02-02 09:33:53