Vpliv topil in procesnih parametrov sušenja z razprševanjem na izdelavo liposomov

Osredkar, Simona (avtor), Zupančič, Špela (mentor), Homar, Miha (komentor)

Liposomi so sferični lipidni vezikli, ki zaradi sposobnosti vgradnje tako hidro- kot tudi lipofilnih učinkovin in tarčne dostave v farmaciji pridobivajo na svoji veljavi kot obetavni nanodostavni sistemi. Eden večjih izzivov je priprava liposomov v industrijskem merilu, kjer sušenje z razprševanjem predstavlja izreden potencial. Izhajajoč iz slednjega, je bil cilj magistrske naloge ovrednotiti vpliv različnih topil in parametrov sušenja z razprševanjem na izdelavo liposomov s predhodno določeno sestavo, s čimer bi pridobili pomembne podatke o možnosti prenosa metode izdelave na proizvodno raven. Na podlagi literature in eksperimentov smo poiskali primerno topilo za raztapljanje fosfolipidov (distearoilfosfatidilholin (DSPC), natrijeva sol distearoilfosfatidilglicerol (DSPG-Na)) in holesterola. Liposome smo izdelali tako, da smo raztopino pomožnih snovi sušili z razprševanjem pri različnih parametrih (hitrost razprševanja, hitrost in temperatura vstopnega zraka). Vmesni produkt smo nato rehidrirali z vodnim medijem ter nastale liposome ekstrudirali skozi polikarbonatno membrano. Na vmesnem produktu smo izvedli termično analizo, liposomom pa smo izmerili hidrodinamski premer, polidisperzni indeks in zeta potencial. Pri eksperimentalnem delu in analizi podatkov smo upoštevali princip načrtovanja eksperimentov, ki nam omogoča, da na majhnem številu eksperimentov dobimo maksimalno količino informacij za ovrednotenje procesa in končnega produkta. Glede na topnost pomožnih snovi in ICH smernic smo za pripravo disperzije izbrali dve topili: mešanico diklorometana in metanola v volumskem razmerju 1:1 in metanol. Proces raztapljanja DSPG-Na v topilih pa smo pospešili s segrevanjem disperzije na 40 °C. Z analizo nastalih liposomov smo ugotovili, da sta nanje imela vpliv le dva parametra sušenja z razprševanjem. Pri nižji hitrosti pretoka zraka dobimo večji izkoristek procesa, če zvišamo temperaturo vstopnega zraka po redispergiranju suhega produkta, pa dobimo manjše liposome. Premer začetnih liposomov se je s približno 800 nm po ekstruziji zmanjšal na 150 nm, medtem ko je bil zeta potencial v obeh primerih praktično enak. Z metodo termične analize vzorcev smo dokazali tudi odsotnost zaostanka topil v suhem produktu. Ključna ugotovitev magistrskega dela je, da se z ekstruzijo liposomov vplivi parametrov sušenja z razprševanjem na velikost in porazdelitev velikosti liposomov izničijo.

• Jezik: Slovenski jezik
• Ključne besede: liposomi, princip načrtovanja eksperimentov, topila, sušenje z razprševanjem, procesni parametri
• Vrsta gradiva: Magistrsko delo/naloga
• Organizacija: FFA - Fakulteta za farmacijo
• Leto izida: 2020
• PID: 20.500.12556/RUL-124071
• Datum objave v RUL: 24.12.2020

OSREDKAR, Simona, 2020, Vpliv topil in procesnih parametrov sušenja z razprševanjem na izdelavo liposomov [na spletu]. Magistrsko delo. [Dostopano 23 marec 2025]. Pridobljeno s: https://repozitorij.uni-lj.si/IzpisGradiva.php?lang=slv&id=124071

Sekundarni jezik

• Jezik: Angleški jezik
• Naslov: Impact of solvents and spray drying process parameters on liposome production

Izvleček

Liposomes are spherical lipid vesicles constantly gaining ground in drug development as potential drug nanodelivery systems due to their ability to incorporate hydrophilic as well as lipophilic active ingredients. One of the major challenges is liposome production on an industrial scale where spray drying offers great potential. Stemming from the latter, the aim of this master's thesis was to evaluate the effects of different solvents and spray drying parameters on the production of liposomes with predetermined composition in order to obtain information on the possibility of transferring method to the production level. Based on literature and experiments we found suitable solvents for dissolving phospholipids (distearoyl phosphatidylcholine.(DSPC), distearoyl phosphatidylglycerole sodium salt (DSPG-Na)) and cholesterol. Liposomes were prepared by spray drying the lipid dispersion at varying parameters (air flow rate, feed rate and inlet temperature). The spray dried product was rehydrated in aqueous medium and the resulting liposomes were extruded through polycarbonate membrane. Thermal analysis was performed on spray dry powder and hydrodynamic diameter, polydispersity index and zeta potential of liposomes were measured. In experimental work and data analysis, we followed the principle of experimental design which allows us to obtain maximum amount of information for process and end product evaluation on a small number of experiments. Based on excipients solubility and ICH guidelines two solvents were selected for spray drying experiments: a mixture of dichloromethane and methanol in 1:1 volume ratio and methanol. The process of dissolving DSPG-Na was accelerated by heating the dispersion to 40 °C. By analysing the resulting liposomes, we found that their properties were influenced by two spray drying parameters. Higher process yield was obtained at lower air flow rate and smaller liposomes were obtained if the inlet gas temperature was raised. The diameter of the resulting liposomes was about 800 nm and decreased to 150 nm after extrusion, while zeta potential remained the same in both cases. The absence of solvent residue in dry product was proved by thermal analysis of samples. The key finding of the master's thesis was that by extrusion of liposomes the effects of spray-drying parameters on the size and polydispersity index of liposomes are practically eliminated.

• Ključne besede: liposomes, design of experiment, solvents, spray drying, process parameters