Title Liofilizacija nanosuspenzije melatonina uz dodatak krioprotektora Title (english) Freeze-drying of melatonin nanosuspension in the presence of a cryoprotectant Author Tin Rogina Mentor Anita Hafner (mentor)Committee member Anita Hafner (predsjednik povjerenstva)Committee member Lidija Bach-Rojecky (član povjerenstva)Committee member Laura Nižić Nodilo (član povjerenstva)Granter University of Zagreb Defense date and country 2024-08-28, Croatia Scientific / art field, BIOMEDICINE AND HEALTHCARE Abstract Melatonin je hormon lipofilnog karaktera i ograničene topljivosti u vodi koji u ljudskom organizmu fiziološki sintetizira epifiza. Ostvaruje pleiotropni učinak na glavne fiziološke funkcije, stanični ciklus i biokemijske mehanizme s cirkadijanim obilježjima. Terapijska primjena se primarno odnosi na poremećaje spavanja poput nesanice. Suvremena istraživanja usmjerena su na razvoj inovativnih farmaceutskih oblika melatonina. Izrada nanosuspenzija predstavlja jednu od strategija oblikovanja slabo
... More topljivih lijekova s ciljem povećanja topljivosti, brzine otapanja i bioraspoloživosti. Međutim, glavno ograničenje je dugoročna nestabilnost nanosuspenzija i sklonost čestica agregaciji. Sušenje smrzavanjem, odnosno liofilizacija, pokazalo se kao jedna od metoda razvoja čvrstih oblika nanosuspenzija povećane fizičke stabilnosti. Cilj ovog rada bio je ispitati mogućnost liofilizacije nanosuspenzije melatonina u svrhu razvoja suhog oblika koristeći glukozu, manitol i trehalozu (0,5 – 2,5 %, m/V) kao krioprotektore, te ispitati njihov utjecaj na kratkoročnu i dugoročnu stabilnost razvijenih liofilizata mjereći veličinu, indeks polidisperznosti i zeta-potencijal nanokristala u rekonstituiranim suspenzijama. Nanosuspenzija melatonina (0,143 %, m/V) pripravljena je metodom vlažnog mljevenja uz dodatak polisorbata 80 (0,286 %, m/V) kao površinski aktivne tvari, u masenom omjeru 1:2. Veličina čestica ishodne nanosuspenzije iznosila je 176,4 ± 3,3 nm uz indeks polidisperznosti od 0,141 ± 0,013. Liofilizacija nanosuspenzije melatonina uz dodatak manitola rezultirala je liofilizatom volumena jednakog volumenu suspenzije prije liofilizacije. U slučaju trehaloze uočen je djelomični kolaps, a u slučaju glukoze potpuni kolaps strukture liofilizata. Manitol i trehaloza su pri koncentracijama od 0,5 do 2,5 % (m/V) osigurali zadovoljavajuće očuvanje fizičkih svojstava nanokristala melatonina nakon liofilizacije, za razliku od glukoze. Porastom koncentracije manitola i trehaloze u liofiliziranoj nanosuspenziji djelomično se povećala uspješnost očuvanja veličine i raspodjele veličina nanokristala. Tijekom skladištenja pri 4 °C u razdoblju od 60 dana, uz manitol i trehalozu (2,5 %, m/V) kao krioprotektore, uspješno su sačuvani izgled liofilizata i fizička svojstva nanokristala nakon rekonstitucije, čime je potvrđen njihov krioprotektivni učinak u procesu liofilizacije nanosuspenzije melatonina. Less Abstract (english) Melatonin is a lipophilic hormone with limited water solubility, which is physiologically synthesized in the human body by the pineal gland. It has a pleiotropic effect on the main physiological functions, the cell cycle, and biochemical mechanisms with circadian characteristics. Therapeutic use is primarily related to sleep disorders such as insomnia. Nowadays, research is focused on the development of innovative pharmaceutical forms of melatonin. The production of nanosuspensions represents
... More one of the strategies for the formulation of poorly soluble drugs with the aim of increasing their solubility, dissolution rate and bioavailability. However, the main limitation is the long-term instability of nanosuspensions and the tendency of particles to aggregate. Freeze drying, i.e. lyophilisation, proved to be one of the methods of developing solid forms of nanosuspensions with increased physical stability. The aim of this work was to examine the possibility of lyophilisation of melatonin nanosuspension for the purpose of developing a dry form using glucose, mannitol and trehalose (0.5-2.5%, w/v) as cryoprotectants, and to examine their influence on the short-term and long-term stability of the developed lyophilisates by measuring size, polydispersity index and zeta-potential of nanocrystals in reconstituted suspensions. Nanosuspension of melatonin (0.143%, w/v) was prepared by the method of wet milling with the addition of polysorbate 80 (0.286%, w/v) as a surfactant, in a weight ratio of 1:2. The particle size within the initial nanosuspension was 176.4 ± 3.3 nm with a polydispersity index of 0.141 ± 0.013. Lyophilisation of the melatonin nanosuspension in the presence of mannitol resulted in a lyophilisate volume equal to the volume of the suspension before lyophilisation. In the case of trehalose, a partial collapse was observed, and in the case of glucose, a complete collapse of the structure of the lyophilisate was observed. Mannitol and trehalose at concentrations from 0.5 to 2.5 % (w/v) ensured satisfactory preservation of the physical properties of melatonin nanocrystals after lyophilisation, in contrast to glucose. Increasing the concentration of mannitol and trehalose in the lyophilised nanosuspension partially increased the success of preserving the size and size distribution of nanocrystals. During storage at 4 °C for a period of 60 days, with mannitol and trehalose (2.5 %, w/v) as cryoprotectants, the appearance of the lyophilisate and the physical properties of the nanocrystals after reconstitution were successfully preserved, thus confirming their cryoprotective effect in the process of lyophilisation of melatonin nanosuspensions. Less Keywords
melatonin
nanosuspenzije
liofilizacija
krioprotektor
glukoza
manitol
trehaloza
Keywords (english)
melatonin
nanosuspensions
lyophilisation
cryoprotectant
glucose
mannitol
trehalose
Language croatian URN:NBN urn:nbn:hr:163:627813 Study programme Title: Pharmacy - integrated undergraduate and graduate - university study Type of resource Text File origin Born digital Access conditions Open access Terms of use Created on 2024-10-18 13:04:29
