Optimizacija elektrostatskega razprševanja za izdelavo polietilenglikolnih delcev z vgrajenim simvastatinom s pristopom načrtovanja eksperimentov

Metličar, Klara (author), Zupančič, Špela (mentor), Sterle Zorec, Barbara (comentor)

Polimerni nanodelci so majhni delci velikosti od 1 do 100 nm, širše gledano do 1000 nm, sestavljeni iz polimernih materialov. V farmaciji zaradi svojih lastnosti in potencialnih koristi predstavljajo perspektivne dostavne sisteme. Z metodo elektrostatskega razprševanja je možno izdelati polimerne delce, ki zdravilno učinkovino transformirajo v amorfno stanje, kar izboljša metastabilno topnost učinkovine in s tem njeno biološko uporabnost. Naš namen je bil razviti polimerne nanodelce iz polietilenglikola in vanje vgraditi simvastatin z elektrostatskim razprševanjem. Na začetku smo preverjali topnost zdravilne učinkovine in polietilenglikola v različnih organskih topilih. Nato smo iz izbranih topil izdelali polimerne delce z metodo elektrostatskega razprševanja. S pomočjo načrta eksperimentov smo preučevali vpliv molekulske mase polimera, koncentracijo polimerne raztopine, volumski pretok in delež vgrajenega simvastatina na velikost delcev. Morfologijo, velikost in porazdelitev velikosti delcev smo vrednotili s pomočjo slik, posnetih z vrstičnim elektronskim mikroskopom, in uporabo programov ImageJ, Excel in Minitab. Izmed desetih različnih organskih topil se je etanol glede na topnost polimera in učinkovine, varnost, stabilnost elektrostatskega razprševanja in morfologijo delcev izkazal kot najprimernejši. S pomočjo načrta eksperimentov smo ugotovili, da na velikost delcev najbolj vpliva volumski pretok, na stabilnost procesa pa koncentracija polimerne raztopine. Sferične delce z velikostjo 0,74 µm smo izdelali s 13 % (m/V) raztopino polietilenglikola (35.000 g/mol) pri pretoku 600 µL/h. S pomočjo funkcije »Response Optimizer« pa smo identificirali najoptimalnejše pogoje za pripravo najmanjših delcev in vanje uspešno vgradili različne vsebnosti simvastatina. Ugotovili smo, da manjša kot je vsebnost simvastatina, bolj kvalitetne, gladke in sferične delce izdelamo, ki so med sabo tudi manj zliti. Čeprav smo si zastavili, da bomo izdelali nanodelce, smo se ves čas magistrskega dela gibali na meji med nano- in mikrodelci. Cilj magistrske naloge je bil dosežen z uspešno izdelavo polietilenglikolskih delcev z vgrajenim simvastatinom.

• Language: Slovenian
• Keywords: polimerni delci, elektrostatsko razprševanje, načrtovanje eksperimentov, velikost delcev, porazdelitev velikosti delcev, polietilenglikol, simvastatin.
• Work type: Master's thesis/paper
• Organization: FFA - Faculty of Pharmacy
• Year: 2024
• PID: 20.500.12556/RUL-159328
• Publication date in RUL: 06.07.2024

Secondary language

• Language: English
• Title: Optimising electrospraying process for the preparation of simvastatin-loaded polyethylene glycol particles using an experimental design approach

Abstract

Polymeric nanoparticles are small particles that ranges between 1 to 1000 nm, and are made of polymeric materials. In the pharmaceutical field, they represent a promising delivery system due to their unique properties and potential benefits. The electrospraying method allows for the production of polymeric nanoparticles that can convert a drug into an amorphous state, thereby enhancing its metastable solubility and, consequently, its bioavailability. Our goal was to polymeric nanoparticles using polyethylene glycol with incorporated simvastatin through the electrospraying method. In the first step, we tested the solubility of the drug and polyethylene glycol in various organic solvents. Next, we used electrospraying to produce polymer particles from the selected solvents. Using a design of experiments, we analyzed how factors such as polymer molecular weight, polymer solution concentration, volume flow rate, and the proportion of simvastatin affect particle size. We examined the morphology, size, and size distribution of the particles using images captured with a scanning electron microscope, and then analyzed them with ImageJ, Excel, and Minitab software. Out of 10 different organic solvents, ethanol proved to be the most suitable for polymer and drug solubility, safety, electrospraying stability, and particle morphology. Our design of experiments analysis revealed that volumetric flow rate had the greatest impact on particle size, while the stability of the process was primarily influenced by the polymer solution's concentration. Spherical particles measuring 0.74 µm were produced from a 13% (w/v) solution of polyethylene glycol (35,000 g/mol) at a volume flow rate of 600 µL/h. We determined the most optimal conditions for creating the smallest particles and successfully incorporated simvastatin into them at varying concentrations. Our findings show that particles with lower simvastatin content tend to be of higher quality, with smoother, more spherical shapes and less aggregation. Although our original aim was to produce nanoparticles, our results indicate that we often worked at the boundary between nano- and microparticles. The goal of the Master’s degree was achieved with the successful production of polyethylene glycol particles containing simvastatin.

• Keywords: polymeric particles, electrospraying, design of experiments, particle size, particle size distribution, polyethylene glycol, simvastatin