Vpliv formulacijskih in procesnih parametrov na lastnosti posušene emulzije, proizvedene s tehnologijo sušenja z razprševanjem

Pongrac, Marko (author), Dreu, Rok (mentor), Pohlen, Mitja (comentor)

Peroralna pot dostave zdravilnih učinkovin je pri bolnikih še vedno najbolj zaželena. Izziv peroralne aplikacije zdravil, ki vsebujejo slabo vodotopne zdravilne učinkovine, je slaba biološka uporabnost le-teh. Biološko uporabnost slabo vodotopnih lipofilnih učinkovin lahko izboljšamo z uporabo na lipidih osnovanih sistemov, med katere spadajo tudi posušene emulzije. V nalogi smo se lotili izdelave posušene emulzije z modelno zdravilno učinkovino simvastatin. Za pripravo posušene emulzije s simvastatinom smo uporabili proces sušenja z razprševanjem. Z uporabo metode načrtovanja eksperimentov (DOE) in programa Minitab smo v prvi fazi preučili vpliv formulacijskih in procesnih parametrov na lastnosti dobljenih produktov. Vhodni parametri, ki smo jih spreminjali so bili: deleži komponent za pripravo emulzije (delež olja, delež površinsko aktivne snovi, koncentracija nevodnih komponent disperzije), geometrija šobe za razprševanje in tlak razprševanja. V drugi fazi smo na podlagi postavitve modelov in analize poiskali vrednosti parametrov - faktorjev, ki so imeli za rezultat optimalne vrednosti predhodno izbranih kritičnih atributov kakovosti. Parametri, ki smo jih optimizirali so bili: srednja velikost delcev, širina porazdelitve velikosti (span) delcev, maksimalna polnjenost vrtečega bobna, povprečna lomljenost konture površine praška v bobnu, in izkoristek procesa. Za določitev atributov velikosti delcev (srednja vrednost in span) smo uporabili metodo laserske difrakcije, za določitev atributov pretočnih lastnosti (povprečna lomljenost konture površine in maksimalna polnjenost) pa smo uporabili metodo vrtečega bobna. Izkoristek smo izračunali na podlagi bilance mas. Po izdelavi optimiziranih produktov, smo preučevane lastnosti tudi preverili in primerjali z vrednostmi, ki jih je predvidel matematični model. Ugotovili smo, da so naše eksperimentalne vrednosti optimiziranih parametrov precej blizu vrednostim, ki jih je napovedal matematični model. S tem lahko potrdimo ustreznost uporabljenih matematičnih modelov za namene napovedovanja parametrov porazdelitve velikosti delcev, povprečne lomljenosti konture površine, maksimalne polnjenosti in izkoristka procesa sušenja z razprševanjem. Prav tako smo ugotovili, da produkti izkazujejo precej slabe pretočne lastnosti. Za izboljšanje pretočnih lastnosti izdelanih produktov bi tako potrebovali dodatne tehnološke postopke (granulacija, dodatek drsil itd.). S testom raztapljanja smo uspeli potrditi, da se simvastatin iz sušene emulzije sprosti bistveno hitreje in v večjem obsegu v primerjavi s čistim simvastatinom in sproščanjem simvastatina iz generične tablete.

• Language: Slovenian
• Keywords: posušene emulzije, sušenje z razprševanjem, načrtovanje eksperimentov, porazdelitev velikosti, lomljenost konture prašk
• Work type: Master's thesis/paper
• Organization: FFA - Faculty of Pharmacy
• Year: 2020
• PID: 20.500.12556/RUL-121112
• Publication date in RUL: 30.09.2020

PONGRAC, Marko, 2020, Vpliv formulacijskih in procesnih parametrov na lastnosti posušene emulzije, proizvedene s tehnologijo sušenja z razprševanjem [online]. Master’s thesis. [Accessed 24 March 2025]. Retrieved from: https://repozitorij.uni-lj.si/IzpisGradiva.php?lang=eng&id=121112

Secondary language

• Language: English
• Title: The influence of formulation and process parameters on the properties of a dry emulsion prepared with the spray drying technology

Abstract

Oral route of drug administration is still the preferred route among patients. One drawback of the oral application of medication, that contains poorly soluble active ingredients, is the inferior bioavailability of active pharmaceutical ingredients. Bioavailability can be increased by formulating lipophilic active ingredients as lipid-based systems. One option is the preparation of dried emulsions. In the thesis dried emulsions with simvastatin were prepared. Process of spray drying was used to obtain the product. In the first part the design of experiments methodology (DOE) together with Minitab software was used to determine the effect of various formulation and process parameters on the properties of spray dried products. Varied input parameters were: percentages of starting emulsion components (oil component percentage, percentage of surfactants, dispersion concentration), spraying nozzle position and spraying pressure. In the second part of experiments the input parameters that yielded the best results for the previously determined product critical attributes were established, i.e. based on analyzed data and mathematical models. These product attributes were: particles median size, span of particles size distribution, average normalized boarder length, maximum filling of the rotating cylinder and the process yield. To determine the values of particles median size and size distribution span we used the laser diffraction method. Rotating cylinder method was used to determine the flow properties of prepared products. Process yields were calculated from the mass balance before and after the process. After the optimized spray drying products were produced, we analyzed the desired properties and compared them with the values that were predicted by the mathematical model. We found out that the experimental values are similar to the predicted ones. Considering the results we can say that established models are capable of predicting the output values of particles median size, size distribution span, average normalized boarder length, maximum filling ratio and process yield based on the input process and formulation parameters. Also, based on the flow properties data analysis, we concluded that finished products have poor flow properties and would require additional technological processes (e.g. granulation, adding lubricants etc.) to render them usable for pharmaceutical industry applications. With the utilization of dissolution tests we managed to demonstrate that the release of simvastatin is substantially faster and complete in comparison with the pure simvastatin and the release of simvastatin from the generic tablet.

• Keywords: dried emulsions, spray drying process, design of experiments, size distribution, normalised powder border length