Vrednotenje fizikalno-kemijske stabilnosti delcev s simvastatinom, izdelanih z metodo sušenja z razprševanjem za nanos učinkovine s tiskom

Romšak, Gal (avtor), Dreu, Rok (mentor), Sterle Zorec, Barbara (komentor)

Nanašanje zdravilnih učinkovin na biokompatibilne podlage s tehnologijo 2D tiskanja predstavlja inovativen in učinkovit način prilagajanja odmerka zdravilnih učinkovin vsakemu posamezniku. S takim načinom zdravljenja bi lahko uspeli rešiti izzive, ki se pojavljajo zlasti pri zdravljenju kroničnih bolezni, pri zdravljenju otrok in starostnikov ter pri visokopotentnih učinkovinah in/ali učinkovinah z ozkim terapevtskim oknom. Pomembna prednost tehnologije 2D tiskanja se kaže tudi v možnosti priprave farmacevtske oblike neposredno pred izdajo bolniku z dispergiranjem suhih delcev v osnovnem mediju črnila in njihovim tiskanjem na biokompatibilne podlage. Zato je bil cilj našega raziskovalnega dela pripraviti suhe delce s simvastatinom z metodo sušenja z razprševanjem, ki bi bili primerni za dispergiranje v mediju črnil in bi ostali fizikalno-kemijsko dovolj stabilni tekom celotnega obdobja uporabe. Izdelali smo tri različne emulzije z laktozo, kalcijevim silikatom in kombinacijo laktoze in nanoceluloze kot antiadhezivi. Delce smo pripravili z metodo sušenja z razprševanjem omenjenih emulzij, pri čemer je prišlo do pretvorbe simvastatina v amorfno obliko, kar smo potrdili z diferenčno dinamično kalorimetrijo in z infrardečo spektroskopijo s Fourierjevo transformacijo. Pripravili smo delce brez in z dodatkom askorbinske kisline, da bi preverili vpliv antioksidanta na kemijsko stabilnost simvastatina v delcih. Delce smo dispergirali v treh medijih, ki so vsebovali različne deleže propilen glikola in vode. Opravili smo enomesečno stabilnostno študijo pri čemer smo suhe in dispergirane delce shranili pri 25 °C in 40 % RV ter pri 40 °C in 75 % RV. Vzorce smo analizirali s tekočinsko kromatografijo ultra visoke ločljivosti ter določili vsebnost simvastatina v delcih. Ugotovili smo, da dodatek askorbinske kisline pomembno vpliva na kemijsko stabilnost delcev, ki smo jih pripravili z uporabo laktoze ter s kombinacijo laktoze in nanoceluloze. Omenjeni delci po enem mesecu shranjevanja izkazujejo zadovoljivo kemijsko stabilnost. Svežim in dispergiranim delcem smo z lasersko difrakcijo izmerili velikost ter z vrstičnim elektronskim mikroskopom ovrednotili njihove morfološke lastnosti. Zanimal nas je vpliv lokacije vzorčenja, uporabljenega antiadheziva, medija ter temperature shranjevanja na velikost dispergiranih delcev, saj je le-ta ključna, da ne prihaja do neželenega mašenja šob glave tiskalnika. Potrdimo lahko, da ustrezno velikost in fizikalno-kemijsko stabilnost izkazujejo predvsem delci s kombinacijo laktoze in nanoceluloze, ki vsebujejo antioksidant in so dispergirani v najbolj viskoznem mediju.

• Jezik: Slovenski jezik
• Ključne besede: sušenje z razprševanjem, fizikalno-kemijska stabilnost, antiadhezivi, antioksidant, nanos učinkovine s tiskom
• Vrsta gradiva: Magistrsko delo/naloga
• Organizacija: FFA - Fakulteta za farmacijo
• Leto izida: 2023
• PID: 20.500.12556/RUL-144234
• Datum objave v RUL: 05.02.2023

ROMŠAK, Gal, 2023, Vrednotenje fizikalno-kemijske stabilnosti delcev s simvastatinom, izdelanih z metodo sušenja z razprševanjem za nanos učinkovine s tiskom [na spletu]. Magistrsko delo. [Dostopano 21 april 2025]. Pridobljeno s: https://repozitorij.uni-lj.si/IzpisGradiva.php?lang=slv&id=144234

Sekundarni jezik

• Jezik: Angleški jezik
• Naslov: Evaluation of physicochemical stability of simvastatin-containing particles prepared by spray drying for drug deposition by printing

Izvleček

Applying active pharmaceutical ingredients to biocompatible substrates using 2D printing technology is an innovative and effective way to customise the dosage of active pharmaceutical ingredients to each individual. This treatment modality could address the challenges that arise in particular in the treatment of chronic diseases, in the treatment of children and the elderly, and in the treatment of high-potency active substances and/or active substances with a narrow therapeutic window. Another important advantage of 2D printing technology is the possibility to prepare the dosage form immediately prior to dispensing to the patient by dispersing the dry particles in the base ink medium and printing them on biocompatible substrates. Therefore, the aim of our research work was to prepare simvastatin dry particles by spray-drying which are suitable for dispersion in the ink media and remain sufficiently physicochemically stable over the entire shelf life. Three different emulsions were produced with lactose, calcium silicate and a combination of lactose and nanocellulose as anti-adhesives. The particles were prepared by spray-drying of the emulsions and the conversion of simvastatin to an amorphous form which was verified by differential scanning calorimetry and Fourier transform infrared spectroscopy. Particles were prepared without and with the addition of ascorbic acid in order to verify the effect of the antioxidant on the chemical stability of simvastatin in the particles. The particles were dispersed in three media containing different proportions of propylene glycol and water. A stability study was carried out for one month, where both dry and dispersed particles were stored at 25 °C and 40 % RH and at 40 °C and 75 % RH. The samples were analysed by ultra-high performance liquid chromatography and the particle content of simvastatin was determined. We found that the addition of ascorbic acid had a significant effect on the chemical stability of the particles prepared using lactose and a combination of lactose and nanocellulose. These particles show satisfactory chemical stability after 1 month of storage. The fresh and dispersed particles were measured for size by laser diffraction and their morphological properties were evaluated by scanning electron microscopy. We were interested in the influence of the sampling location, the used anti-adhesive, the medium and the storage temperature on the size of the dispersed particles, since it is crucial to avoid unwanted lubrication of the printer head nozzles. It can be confirmed that the particles with the combination of lactose and nanocellulose, which contain an antioxidant and are dispersed in the most viscous medium, show the appropriate size and physico-chemical stability.

• Ključne besede: spray-drying, physicochemical stability, anti-adhesives, antioxidant, drug deposition by printing