Razvoj delcev z učinkovino z metodo sušenja z razprševanjem za ex tempore pripravo kartuš, namenjenih tiskanju v dvorazsežnem prostoru

Grabar, Timotej (avtor), Dreu, Rok (mentor), Sterle Zorec, Barbara (komentor)

Težnja po posamezniku prilagojenemu načinu zdravljenja se iz leta v leto povečuje, saj se potek bolezni in fiziološke lastnosti posameznih bolnikov razlikujejo. Zato si v prihodnosti želimo čimbolj upoštevati specifičnost vsakega posameznika in odmerke zdravil prilagoditi s pomočjo posamezniku prilagojenih farmacevtskih izdelkov. Eden izmed pristopov izdelave takih izdelkov je tudi uporaba tehnologije 2D tiskanja pri ex tempore pripravi, ki predstavlja realno možnost prilagajanja odmerka nizkoodmernih učinkovin. V nalogi smo iz emulzije s kloroformom izdelali delce, ki so vsebovali zdravilno učinkovino simvastatin in polimer polikaprolakton in pri tem zasledovali doseganje najmanjših možnih velikosti delcev. Delce smo izdelali s postopkom sušenja z razprševanjem pri nastavitvah procesnih parametrov, določenih z eksperimentalnim načrtom, in jih kasneje dispergirali v različnih zmeseh propilen glikola in vode. Na podlagi rezultatov eksperimentalnega načrta in vzporedno še z uporabo nevronskih mrež smo poskušali najti optimalno kombinacijo procesnih parametrov. Po prvotni uporabi laktoze, z namenom zmanjšanja adhezije med delci, smo poskušali pod enakimi pogoji izdelati še delce s kalcijevim silikatom ter delce s kombinacijo nanoceluloze in laktoze. S pomočjo vrstične elektronske mikroskopije smo ugotovili, da se tako izdelani delci glede na morfološke lastnosti med seboj bistveno razlikujejo, saj so delci ob prisotnosti laktoze in le-te v kombinaciji z nanocelulozo sprijeti v grozde, medtem ko so po dodatku kalcijevega silikata v emulzijo za razprševanje samostojni. Kljub podobnim velikostnim razredom izdelanih delcev, smo tekom dispergiranja zaznali pomembne razlike. Grozdi delcev z laktozo so se zmanjšali kot posledica raztapljanja laktoze, medtem ko so grozdi izdelani s kombinacijo nanoceluloze in laktoze razpadli do osnovnih delcev grozda kot posledica ločitve antiadheziva od polimernega delca s simvastatinom. Produkt s kalcijevim silikatom ni izkazoval nobenih posebnosti, saj so delci po dispergiranju ostali podobnih velikosti kot v suhi obliki. Istočasno smo vrednotili še vpliv različnih načinov dispergiranja, hranjenja dispergiranega vzorca (en mesec, sobni pogoji, nizka vlažnost) in različnih viskoznosti medija za dispergiranje na velikost dispergiranih delcev. Ustrezna kombinacija procesnih parametrov izdelave je bila ugotovljena z modelom, ki je bil osnovan z eksperimentalnim načrtom. Primeren produkt za uporabo v kartušah za tiskanje je tisti, ki vsebuje zmes nanoceluloze in laktoze in ga dispergiramo v mediju z 90 vol. % propilen glikola.

• Jezik: Slovenski jezik
• Ključne besede: Sušenje z razprševanjem, eksperimentalni načrt, nevronske mreže, disperzibilnost v mediju, kartuše za tiskanje.
• Vrsta gradiva: Magistrsko delo/naloga
• Organizacija: FFA - Fakulteta za farmacijo
• Leto izida: 2021
• PID: 20.500.12556/RUL-125422
• Datum objave v RUL: 16.03.2021

Sekundarni jezik

• Jezik: Angleški jezik
• Naslov: Development of drug loaded particles for ex tempore preparation of cartridges for two-dimensional printing via spray drying method

Izvleček

Therapy timeline of numerous diseases and physiological characteristics differ among individuals. The future goal is to consider specifics of each patient and to modify the medicine doses with the use of individual adjusted pharmaceutical products. One of such approaches is also the introduction of two-dimensional printing technology by ex tempore preparation, which can provide real-time dose adjustment of the low-dose APIs. In our work we produced particles consisting of a drug simvastatin and polymer polycaprolactone and monitored reaching the particles of smallest possible size. Particles were prepared by spray drying an emulsion with chloroform as an organic phase and lactose as an antiadhesive material. A spray-drying process parameters giving the smallest particles were determined by using design of experiment. Later, the particles were dispersed in a liquid mixture of propylene glycol and water. The existence of any other process parameters combination, that could result even in smaller particles, was researched using artificial neural network. Our aim was also minimizing adhesion between particles, so other substances like calcium silicate and combination of nanocellulose and lactose were tested in order to examine their influence on size of produced particles. Using scanning electron microscope we found important differences in particle morphology. Smaller particles produced in the presence of lactose and combination of it with nanocellulose were joined into the bigger clusters, while adding calcium silicate in spraying emulsion contributed to individual particles appearing. Despite of similar particle size ranges of each group, we found an important differences also after their dispergation in the medium. Particle clusters of lactose decreased in size due to dissolution of lactose, when the particle clusters produced with combination of nanocellulose and lactose fell apart to individual particles what probably appeared due to the separation of antiadhesive substance from the polymer particle with simvastatin. After dispergation of calcium silicate particles they showed no significant differences in particle size. Parallelly, we evaluated also the influence of different dispergation ways, different liquid mixture viscosity and sample storage for 1 month at room conditions with low humidity to dispersed particle size differences. The appropriate combination of process parameters to reach smallest particle size was established by design of experiment. Potential suitable particles for usage in printing cartridges includes combination of nanocellulose and lactose and are dispersed in liquid mixture containing 90 vol. % of propylene glycol.

• Ključne besede: Spray drying, design of experiments, artificial neural network, dispersibility in medium, printing cartridges.