| Abstract | Alginati su prirodni polimeri koji se zbog svojih poželjnih svojstava uvelike koriste u farmaceutskoj industriji. Novija istraživanja biofarmaceutske primjene alginata usmjerena su k razvoju alginatnih terapijskih sustava s modificiranim oslobađanjem djelatne tvari. Sušenje raspršivanjem jedna je od najčešće korištenih metoda u pripravi takvih terapijskih sustava jer optimiranje procesnih i formulacijskih parametara omogućuje dobivanje čestica željenih fizičko-kemijskih i biofarmaceutskih svojstava.
Cilj ovog rada bio je provesti fizičko-kemijsku karakterizaciju triju različitih tipova alginata (Manucol® LKX, Protanal® CR 8133 i Protanal® CR 8223) kao ishodnih polimera, i mikročestica pripravljenih sušenjem raspršivanjem polimernih otopina, a u svrhu optimiranja procesa sušenja i svojstava dobivenog suhog produkta. Uz alginate karakteriziran je i polivinilni alkohol PVA 18-88 (PVA) kao polimer koji se može kombinirati s alginatima u izradi mikročestica željenih biofarmaceutskih svojstava. Sušenje raspršivanjem provedeno je na uređaju ProCepT uz upotrebu ultrazvučne sapnice, konusne kolone za sušenje i srednjeg ciklona s padom tlaka od približno 20 mbar, pri brzini peristaltičke pumpe za dovod uzorka 20%, snazi ultrazvučne sapnice 97%, brzini ulaznog zraka za sušenje 0,25 m3/min i temperaturi ulaznog zraka 120 °C za alginate i 150 °C za PVA. Odabrana konfiguracija uređaja te postavke parametara rezultirali su nedovoljnim sušenjem produkta, što je potrebno uzeti u obzir u sljedećim fazama razvoja. Iskorištenja procesa sušenja bila su u rasponu od 24,69 do 55,27%. Sadržaj vlage u alginatnim mikročesticama kretao se između 10,66 i 11,95%, te je odgovarao količini adsorbirane/apsorbirane vlage na ishodne polimere pri temperaturi od 25 °C i relativnoj vlažnosti od 40%. Relativno velik sadržaj vlage alginatnih mikročestica posljedica je nakupljanja atmosferske vlage nakon sušenja raspršivanjem. Sadržaj vlage u PVA mikročesticama iznosio je 2,52%. Sušenje raspršivanjem otopine polimera PVA rezultiralo je njegovom amorfizacijom, dok su alginati bili amorfne strukture i prije sušenja raspršivanjem. Srednji promjer alginatnih mikročestica kretao se uzmeđu 7,9±2,3 μm i 9,3±2,4 μm. U slučaju PVA mikročestica, uočena je bimodalna raspodjela veličina čestica, sa srednjim promjerom od 15,6±8,1 μm. Alginatne mikročestice sferičnog su oblika i uvrnute površine. PVA mikročestice imaju glatku i ravnu površinu, ali su primjećene i one s rupturama i uvrnućima. Rezultati provedenih analiza korisni su za daljnje optimiranje procesa sušenja raspršivanjem i razvoj mikročestica kao terapijskih sustava temeljenih na alginatu. |
| Abstract (english) | Alginate is a natural polymer that is widely used in pharmaceutical industry due to its favorable properties. Current research is directed towards the development of alginate based controlled-release drug delivery systems. Spray-drying is one of the most widely used methods for the preparation of such drug delivery systems since optimisation of the process and formulation parameters enables the preparation of particles with desirable physico-chemical and biopharmaceutical properties.
The aim of this work was to determine physico-chemical properties of three different alginates (Manucol® LKX, Protanal® CR 8133 i Protanal® CR 8223), as well as alginate microparticles prepared by spray-drying of polymer solutions, with the aim to optimise the spray-drying process and the properties of the dry product. Besides alginates, another polymer, polyvinyl alcohol PVA 18-88 (PVA) was characterised since it can be combined with alginates in order to obtain microparticles with desired biopharmaceutical properties. Spray-drying was performed using the ProCepT spray-dryer with the ultrasonic nozzle, standard conical process column and medium cyclone with pressure fall of 20 mbar, at peristaltic pump speed of 20%, ultrasonic nozzle power of 97%, inlet air flow of 0,25 m3/min, inlet air temperature of 120 °C for alginate samples and 150 °C for PVA sample. The spray-dryer configuration and the process parameters employed resulted in insufficient drying of the product, which should be considered in the following stages of the formulation development. Process yield was in range from 24,69 to 55,27%. The moisture content of the spray-dried alginate microparticles was in range from 10,66 to 11,95% and it was consistent with vapour sorption on constitutive polymers at temperature of 25 °C and 40% of relative humidity. Relatively high moisture content of alginate microparticles was a result of the sorption of atmospheric moisture after the spray-drying process. The moisture content in PVA microparticles was 2,52%. Spray-drying of PVA solution resulted in amorphisation of the polymer material while alginates had an amorphous structure even before spray-drying. The mean diameter of alginate microparticles was in the range from 7,9±2,3 μm to 9,3±2,4 μm. For PVA microparticles bimodal size distribution was observed. The mean diametar of PVA microparticles was 15,6±8,1 μm. Alginate microparticles were spherical in shape with buckled surface. Most of PVA microparticles had smooth surface but those with ruptures and pores were also observed. The results of these analyses are useful for the further optimisation of the spray-drying process and the development of alginate-based microparticles as drug delivery systems. |
